NM_170707.4:c.1567G>A

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM1PP3_Strong

The NM_170707.4(LMNA):c.1567G>A(p.Gly523Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000809 in 1,606,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/23 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

LMNA
NM_170707.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:20O:1

Conservation

PhyloP100: 9.92

Publications

29 publications found

Variant links:

Genes affected

LMNA (HGNC:6636): (lamin A/C) The protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]

LMNA Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1A
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet
familial partial lipodystrophy, Dunnigan type
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
Hutchinson-Gilford progeria syndrome
Inheritance: AD, SD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
restrictive dermopathy 2
Inheritance: AR, AD Classification: DEFINITIVE, LIMITED Submitted by: G2P
Emery-Dreifuss muscular dystrophy 2, autosomal dominant
Inheritance: SD, AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
atrioventricular block
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
heart-hand syndrome, Slovenian type
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
Charcot-Marie-Tooth disease type 2B1
Inheritance: AR, AD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
Emery-Dreifuss muscular dystrophy 3, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
mandibuloacral dysplasia with type A lipodystrophy
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
atrial fibrillation
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
atypical Werner syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal dominant Emery-Dreifuss muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital muscular dystrophy due to LMNA mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
lethal restrictive dermopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
LMNA-related cardiocutaneous progeria syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive Emery-Dreifuss muscular dystrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
autosomal semi-dominant severe lipodystrophic laminopathy
Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LMNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM1

In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 10 uncertain in NM_170707.4

PP3

MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMNA	NM_170707.4 link	c.1567G>A	p.Gly523Arg	missense_variant	Exon 9 of 12	ENST00000368300.9	NP_733821.1	P02545-1A0A384MQX1
LMNA	NM_005572.4 link	c.1567G>A	p.Gly523Arg	missense_variant	Exon 9 of 10	ENST00000677389.1	NP_005563.1	P02545-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMNA	ENST00000368300.9 link	c.1567G>A	p.Gly523Arg	missense_variant	Exon 9 of 12	1	NM_170707.4	ENSP00000357283.4		P02545-1
LMNA	ENST00000677389.1 link	c.1567G>A	p.Gly523Arg	missense_variant	Exon 9 of 10		NM_005572.4	ENSP00000503633.1		P02545-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000856

AC:

AN:

233624

AF XY:

0.0000946

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.000174

GnomAD4 exome

AF:

0.0000825

AC:

120

AN:

1454642

Hom.:

Cov.:

AF XY:

0.0000788

AC XY:

AN XY:

723212

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33396

American (AMR)

AF:

0.0000230

AC:

AN:

43476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25968

East Asian (EAS)

AF:

0.00

AC:

AN:

39428

South Asian (SAS)

AF:

0.00

AC:

AN:

85326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000104

AC:

115

AN:

1109294

Other (OTH)

AF:

0.0000500

AC:

AN:

60052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.0000655

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000867

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:20Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:10Other:1

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 05, 2021

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Gly523Arg variant in LMNA has been reported in 5 individual with dilated cardiomyopathy (DCM; Millat 2009 PMID: 19318026, Fichna 2018 PMID: 29970176, LMM data), 1 individual with limb-girdle muscular dystrophy (Magri 2015 PMID: 26404900), 1 individual with LVNC, conduction system disease and muscle weakness (LMM data), and in 2 siblings presenting with features of COL6A2 related myopathy as well as Emery-Dreifuss muscular dystrophy (Chapon 2008, conference abstract only). In the family described by Chapon et al, the myopathy present in both sibs was believed to be due recessively inherited COL6A2 variants. The LMNA variant was present in one of the sibs as well as the father, who was clinically normal but showed dystrophic changes as well as mild deficit of collagen 6 fibers. This variant has also been reported by other clinical laboratories in ClinVar (Variation ID: 48045 ) and has been identified in 0.01% (8/68028) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PP3. -

Feb 05, 2025

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Observed to segregate with DCM, conduction disease, and/or subtle right ventricular abnormalities in individuals from one family, but was also observed in unaffected individuals in this family (PMID: 30919684); Published functional studies demonstrate altered ability of LMNA protein to interact with 5% of its protein targets; however, it is unclear how these studies may translate to a pathogenic role in vivo (PMID: 24623722); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24375749, 24503780, 24846508, 21846512, 26404900, 25163546, 28663758, 28679633, 27576561, 26633542, 29970176, 31744510, 32193531, 31383942, 32041611, 34495297, 34862408, 38979608, 24623722, 37425136, 37624850, 19318026, 35026164, 31476771, 36397776, 34720847, 32826072, 29961767, 30919684, 10939567, 37652022) -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 19, 2022

Revvity Omics, Revvity

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Epithelial Biology; Institute of Medical Biology, Singapore

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 16, 2018

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Cardiomyopathy

Uncertain:2

Jul 31, 2024

Color Diagnostics, LLC DBA Color Health

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces glycine with arginine at codon 523 of the LMNA protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. An experimental study using a yeast two hybrid system has shown that this variant may lead to ~5% lost protein interactions (PMID: 24623722), but functional and clinical significance of this observation is not known. This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 19318026, 21846512, 24503780, 29961767, 30919684, 31383942, 38979608), in an individual affected with hypertrophic cardiomyopathy (PMID: 35026164), and in individuals affected with limb girdle muscular dystrophy (PMID: 26404900, 34720847). This variant has been reported in four members of one family (PMID: 30919684); one carrier was affected with subtle right ventricular abnormalities, and the carrier's parent was affected with dilated cardiomyopathy and conduction disease. This variant has also been reported in individuals affected with laminopathy (PMID: 28663758, 31744510, 32193531, 32826072), in individuals affected with chronic kidney disease (PMID: 31383942), and in multiple apparently healthy individuals in a large biobank (PMID: 31383942). This variant has been identified in 22/264998 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

Jul 08, 2022

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Uncertain:2

Apr 10, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.G523R variant (also known as c.1567G>A), located in coding exon 9 of the LMNA gene, results from a G to A substitution at nucleotide position 1567. The glycine at codon 523 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been detected in individuals with dilated cardiomyopathy (DCM) (Pugh TJ et al. Genet. Med., 2014 Aug;16:601-8; Millat G et al. Clin. Biochem., 2009 Jun;42:892-8; Millat G et al. Eur J Med Genet Aug;54:e570-5; Hylind RJ et al. Circ Genom Precis Med. 2019 Mar;12(3):e002463). This variant has also been detected in individuals with limb girdle muscular dystrophy (LGMD); however, in some cases, other variants in myopathy-related genes were also detected (Magri F et al. BMC Neurol, 2015 Sep;15:172; Fichna JP et al. Hum. Genomics, 2018 07;12:34). This variant has also been detected in two individual from familial partial lipodystrophy cohort; however details were limited (Vasandani C et al. J Endocr Soc. 2022 Oct;6(12):bvac155). This variant was also reported in 35 individuals from an electronic medical record review exome cohort, including one DCM case and two individuals with chronic kidney disease (Park J et al. Genet Med, 2020 01;22:102-111). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PS4_supp;PP2;PP3 -

Left ventricular noncompaction

Pathogenic:1

Apr 19, 2017

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

Significance:Likely pathogenic

Review Status:flagged submission

Collection Method:clinical testing

- -

not specified

Uncertain:1

Feb 14, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: LMNA c.1567G>A (p.Gly523Arg) results in a non-conservative amino acid change located in the Lamin tail domain (IPR001322) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.6e-05 in 233624 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in LMNA causing Cardiomyopathy (8.6e-05 vs 0.00025), allowing no conclusion about variant significance. c.1567G>A has been reported in the literature in individuals with dilated cardiomyopathy, limb-girdle muscular dystrophy, dyslipidemia, and EmeryDreifuss muscular dystrophy, without strong evidence of causality (example: Hylind_2019, Millat_2009, Millat_2011, Pugh_2014, Haas_2015, Park_2020, Pena-Pena_2021, Magri_2015, Fichna_2018, Dron_2020, McGurk_2023, Cannie_2023, Boen_2024, Garcia-Pavia_2024). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect (Dittmer_2014). Two studies have shown the variant is unlikely to contribute to disease (Gregory_2023, and Anderson_2021). The following publications have been ascertained in the context of this evaluation (PMID: 38689299, 37639473, 24623722, 32041611, 29970176, 38979608, 37624850, 25163546, 30919684, 26404900, 37652022, 19318026, 21846512, 31383942, 32826072, 24503780,34862408). ClinVar contains an entry for this variant (Variation ID: 48045). Based on the evidence outlined above, the variant was classified as uncertain significance. -

Charcot-Marie-Tooth disease type 2

Uncertain:1

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 523 of the LMNA protein (p.Gly523Arg). This variant is present in population databases (rs201583907, gnomAD 0.01%). This missense change has been observed in individual(s) with limb girdle muscular dystrophy, dilated cardiomyopathy, dyslipidemias, or atrial fibrillation (PMID: 19318026, 24503780, 26404900, 29970176, 32041611, 34495297). ClinVar contains an entry for this variant (Variation ID: 48045). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LMNA protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LMNA function (PMID: 24623722). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Lethal tight skin contracture syndrome

Uncertain:1

Jun 21, 2019

Baylor Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Dilated cardiomyopathy 1A

Uncertain:1

Feb 28, 2020

Johns Hopkins Genomics, Johns Hopkins University

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Primary dilated cardiomyopathy

Uncertain:1

Sep 23, 2024

All of Us Research Program, National Institutes of Health

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces glycine with arginine at codon 523 of the LMNA protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). An experimental study using a yeast two hybrid system has shown that this variant may lead to ~5% lost protein interactions (PMID: 24623722), but functional and clinical significance of this observation is not known. This variant has been reported in individuals affected with dilated cardiomyopathy (PMID: 19318026, 21846512, 24503780, 29961767, 30919684, 31383942), in an individual affected with hypertrophic cardiomyopathy (PMID: 35026164), and in individuals affected with limb girdle muscular dystrophy (PMID: 26404900, 34720847). This variant has been reported in four members of one family (PMID: 30919684); one carrier was affected with subtle right ventricular abnormalities, and the carrier's parent was affected with dilated cardiomyopathy and conduction disease. This variant has also been reported in individuals affected with laminopathy (PMID: 28663758, 31744510, 32193531, 32826072), in individuals affected with chronic kidney disease (PMID: 31383942), and in multiple apparently healthy individuals in a large biobank (PMID: 31383942). This variant has been identified in 22/264998 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. -

Hutchinson-Gilford syndrome;C0410190:Emery-Dreifuss muscular dystrophy 2, autosomal dominant;C0796031:Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome;C1720860:Familial partial lipodystrophy, Dunnigan type;C1854154:Charcot-Marie-Tooth disease type 2B1;C1857829:Heart-hand syndrome, Slovenian type;C2750035:Emery-Dreifuss muscular dystrophy 3, autosomal recessive;C2750785:Congenital muscular dystrophy due to LMNA mutation;C5399785:Mandibuloacral dysplasia with type A lipodystrophy;C5676942:Restrictive dermopathy 2;C5979868:Dilated cardiomyopathy 1A

Uncertain:1

Jun 04, 2024

Fulgent Genetics, Fulgent Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

CardioboostCm

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.99

.;.;.;D;.;.;.;.;D

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;T;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.95

D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.5

M;.;M;M;M;.;.;.;.

PhyloP100

9.9

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.9

D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.96

Sift

Uncertain

0.0010

D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;D;D;D;D

Polyphen

1.0

D;.;D;D;.;.;D;.;.

Vest4

0.99

MutPred

0.86

Gain of MoRF binding (P = 0.0148);.;Gain of MoRF binding (P = 0.0148);Gain of MoRF binding (P = 0.0148);Gain of MoRF binding (P = 0.0148);.;.;.;.;

MVP

0.99

MPC

1.2

ClinPred

0.91

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.92

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over