19-11113329-C-T

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PS4_ModeratePM2PP1PP4

This summary comes from the ClinGen Evidence Repository: NM_000527.5(LDLR):c.1238C>T (p.Thr413Met) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4_Moderate, PP1 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00006533 (0.007%) in South Asian (gnomAD v2.1.1). PS4_moderate - Variant meets PM2. Variant identified in 6 index cases.PP1 - Variant segregates with phenotype in 2 members of family (2 meiosis) from GeneDx laboratory.PP4 - Variant meets PM2. Variant identified in 6 index cases (2 cases from Center of molecular biology and gene therapy with Simon-Broome criteria; 1 case from GeneDx laboratory with Simon Broome criteria, 1 case from Color laboratory with DLCN criteria, 2 cases from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA) with DLCN criteria). LINK:https://erepo.genome.network/evrepo/ui/classification/CA023439/MONDO:0007750/013

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

LDLR
NM_000527.5 missense

Scores

Clinical Significance

Likely pathogenic reviewed by expert panel P:20U:3

Conservation

PhyloP100: 1.71

Publications

10 publications found

Variant links:

Genes affected

LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]

LDLR links:

MIR6886 (HGNC:50121): (microRNA 6886) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6886 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PS4

For more information check the summary or visit ClinGen Evidence Repository.

PM2

For more information check the summary or visit ClinGen Evidence Repository.

PP1

For more information check the summary or visit ClinGen Evidence Repository.

PP4

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDLR	NM_000527.5 link	c.1238C>T	p.Thr413Met	missense_variant	Exon 9 of 18	ENST00000558518.6	NP_000518.1	P01130-1A0A024R7D5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDLR	ENST00000558518.6 link	c.1238C>T	p.Thr413Met	missense_variant	Exon 9 of 18	1	NM_000527.5	ENSP00000454071.1		P01130-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251176

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727094

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

1112004

Other (OTH)

AF:

0.0000994

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.00000658

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000300

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:20Uncertain:3

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Pathogenic:10Uncertain:2

Jan 03, 2017

Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

May 08, 2023

Institute of Human Genetics, University of Leipzig Medical Center

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Criteria applied: PS4_MOD,PM2_SUP,PP1,PP3,PP4 -

Dec 23, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 16, 2016

Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting -

Jun 09, 2021

ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel

Significance:Likely pathogenic

Review Status:reviewed by expert panel

Collection Method:curation

NM_000527.5(LDLR):c.1238C>T (p.Thr413Met) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PS4_Moderate, PP1 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00006533 (0.007%) in South Asian (gnomAD v2.1.1). PS4_moderate - Variant meets PM2. Variant identified in 6 index cases. PP1 - Variant segregates with phenotype in 2 members of family (2 meiosis) from GeneDx laboratory. PP4 - Variant meets PM2. Variant identified in 6 index cases (2 cases from Center of molecular biology and gene therapy with Simon-Broome criteria; 1 case from GeneDx laboratory with Simon Broome criteria, 1 case from Color laboratory with DLCN criteria, 2 cases from Cardiovascular Genetics Laboratory (PathWest Laboratory Medicine WA) with DLCN criteria). -

Oct 23, 2017

Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This c.1238C>T (p.Thr413Met) variant in the LDLR gene has been reported in multiple individuals with familial hypercholesterolemia (PMID: 11857755, 17539906, 19843101, 11668627, 15015036, 25682026) or myocardial infarction (PMID: 25487149). The p.Thr413Met variant occurs within the low-density lipoprotein receptor repeat class B domain of the LDLR protein (https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?seqinput=NP_001182729.1 ). The c.1238C>T variant is rare in the general population and threonine at position 413 of the LDLR protein is highly evolutionarily conserved. The c.1238C>T (p.Thr413Met) variant in the LDLR gene is classified as likely pathogenic. -

Aug 31, 2024

All of Us Research Program, National Institutes of Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 of the EGF precursor homology domain of the LDLR protein. This variant is also known as p.Thr392Met in the mature protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have indicated no significant change in LDLR protein expression and function due to this variant (PMID: 32015373, 34029164). This variant has been reported in over twenty heterozygous individuals affected with familial hypercholesterolemia (PMID: 11668627, 11857755, 15015036, 15199436, 15576851, 17539906, 19843101, 22883975, 25682026, 31993549; ClinVar SCV001960926.1) and in an individual affected with myocardial infarction (PMID: 25487149). This variant has been observed in an individual with severe familial hypercholesterolemia who also carried a pathogenic truncation variant in the same gene (PMID: 34029164). This variant has been reported to segregate with disease in two members of a family (ClinVar SCV001960926.1). This variant has been identified in 7/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Jun 05, 2008

Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 31, 2015

Cardiovascular Biomarker Research Laboratory, Mayo Clinic

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:research

MAF =<0.3%, likely pathogenic based on the integrative in-silico score, previously reported as P/LP in the literature -

Mar 25, 2016

LDLR-LOVD, British Heart Foundation

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:literature only

- -

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PM2_Supporting+PS4_Moderate+PM3+PP4+PS3_Supporting -

not provided

Pathogenic:5

Jan 26, 2022

AiLife Diagnostics, AiLife Diagnostics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 17, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The LDLR c.1238C>T; p.Thr413Met variant (rs368562025) is reported in the literature in multiple individuals affected with familial hypercholesterolemia and myocardial infarction (Do 2015, Dong 2022, eMERGE Consortium 2019, Sturm 2021, Sustar 2022). This variant is also reported as likely pathogenic by an expert panel in ClinVar (Variation ID: 161276). This variant is found in the general population with an overall allele frequency of 0.003% (7/251176 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.692). Based on available information, this variant is considered to be likely pathogenic. References: Do R, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015 Feb 5;518(7537):102-6. PMID: 25487149. Dong W et al. Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia. J Lipid Res. 2022 Jun;63(6):100209. PMID: 35460704. eMERGE Consortium et al. Harmonizing Clinical Sequencing and Interpretation for the eMERGE III Network. Am J Hum Genet. 2019 Sep 5;105(3):588-605. PMID: 31447099. Sturm AC et al. Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. JAMA Cardiol. 2021 Aug 1;6(8):902-909. PMID: 34037665. Sustar U et al. Universal screening for familial hypercholesterolemia in 2 populations. Genet Med. 2022 Oct;24(10):2103-2111. PMID: 35913489. -

Jun 11, 2025

GeneDx

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.(T392M); This variant is associated with the following publications: (PMID: 24055113, 25487149, 11668627, 11857755, 25637381, 15015036, 15576851, 15199436, 17539906, 28145427, 32015373, 32719484, 32522009, 30586733, 31447099, 34037665, 35913489, 34906840, Gratton2023[CaseReport], 37409534, 35460704, 37443404, 25682026, 38740897, 38506081, 22883975, 33854068, 27783906, 38258479) -

Nov 09, 2023

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The LDLR c.1238C>T (p.Thr413Met) variant has been reported in the published literature in several affected individuals with familial hypercholesterolemia (PMIDs: 11857755 (2002), 15199436 (2004), 17539906 (2007), 22883975 (2012), 25682026 (2015), 32522009 (2020), 33854068 (2021), 34029164 (2021), 34037665 (2021), 34906840 (2022), and 35460704 (2022)), coronary artery disease (PMID: 27050191 (2016)), or myocardial infarction (PMID: 25487149 (2015)). A functional study found that LDL-LDLR binding activity and LDL uptake were similar to wild type LDLR, as well as no effect on protein expression in transfected cells (PMID: 32015373 (2020)). The frequency of this variant in the general population, 0.000071 (3/42136 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, this variant is classified as likely pathogenic. -

Jun 25, 2024

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PP1, PP4, PM2, PS3_supporting, PS4_moderate -

Familial hypercholesterolemia

Pathogenic:4

May 09, 2023

Color Diagnostics, LLC DBA Color Health

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This missense variant (also known as p.Thr392Met in the mature protein) replaces threonine with methionine at codon 413 in the LDLR type B repeat 1 of the EGF precursor homology domain of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Functional studies have indicated no significant change in LDLR protein expression and function due to this variant (PMID: 32015373, 34029164). This variant has been reported in over twenty heterozygous individuals affected with familial hypercholesterolemia (PMID: 11668627, 11857755, 15015036, 15199436, 15576851, 17539906, 19843101, 22883975, 25682026, 31993549, 34037665; ClinVar SCV001960926.1). It has also been reported in an individual affected with myocardial infarction (PMID: 25487149) and in an individual affected with low circulating HDL-C (PMID: 35460704). This variant has also been observed in compound heterozygous state with a known pathogenic LDLR variant in an individual affected with severe homozygous familial hypercholesterolemia, a phenotype expected of having two deleterious LDLR variants (PMID: 34029164). This variant has been reported to segregate with disease in two members of a family (ClinVar SCV001960926.1). This variant has been identified in 7/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Likely Pathogenic. -

Aug 13, 2020

Natera, Inc.

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 413 of the LDLR protein (p.Thr413Met). This variant is present in population databases (rs368562025, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 11857755, 20236128, 25682026; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. Invitae Evidence Modeling of clinical and family history, age, sex, and reported ancestry of multiple individuals with this LDLR variant has been performed. This variant is expected to be pathogenic with a positive predictive value of at least 99%. This is a validated machine learning model that incorporates the clinical features of 363,995 individuals referred to our laboratory for LDLR testing. ClinVar contains an entry for this variant (Variation ID: 161276). 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 LDLR protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. -

Dec 12, 2022

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

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: LDLR c.1238C>T (p.Thr413Met) results in a non-conservative amino acid change located in the EGF spacer domain (Dong_2022) 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 2.8e-05 in 253468 control chromosomes (gnomAD and publication data). c.1238C>T has been reported in the literature in individuals affected with Familial Hypercholesterolemia, Myocardial infarction or Coronary artery disease (Bunn_2022, Leren_2004, Taylor_2007, Hooper_2012, Do_2014, Khera_2016, Wald_2016, Saadatagah_2021, Sturm_2021). These data indicate that the variant is likely to be associated with disease. At least one functional study showed LDLR activity (LDL binding and uptake) of this variant determined by flow cytometry and indicated LDL uptake as 85% WT and LDL binding as 80% WT, but no effect on protein expression level in transfected cellls (Galicia-Garcia_2020). Twelve ClinVar submitters (evaluation after 2014) cite this variant as uncertain significance (n=3), likely pathogenic (n=8) and pathogenic (n=1), including one expert panel (ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel) classified it as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. -

Cardiovascular phenotype

Pathogenic:1

Apr 11, 2025

Ambry Genetics

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1238C>T (p.T413M) alteration is located in exon 9 (coding exon 9) of the LDLR gene. This alteration results from a C to T substitution at nucleotide position 1238, causing the threonine (T) at amino acid position 413 to be replaced by a methionine (M). This variant (also referred to as p.T392M in the literature) has been detected in individuals with familial hypercholesterolemia (FH) (Bunn 2002; Leren 2004; Taylor 2007; Safarova 2017). This alteration has also been reported in additional subjects with FH and as a compound heterozygote in a child with features of FH (external communication). This amino acid position is well conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. -

Hypercholesterolemia

Uncertain:1

Jun 01, 2014

CSER _CC_NCGL, University of Washington

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

D;.;.;.;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.96

D;D;D;D;D;D

M_CAP

Pathogenic

0.71

MetaRNN

Pathogenic

0.90

D;D;D;D;D;D

MetaSVM

Pathogenic

0.82

MutationAssessor

Benign

1.5

L;.;.;.;.;L

PhyloP100

1.7

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.8

D;D;D;D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.023

D;D;D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.65

MVP

1.0

MPC

0.80

ClinPred

0.78

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.31

gMVP

0.96

Mutation Taster

=18/82

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over