chr3-38551022-C-T

Position:

chr3-38551022-C-T

Variant summary

Our verdict is Pathogenic. Variant got 15 ACMG points: 15P and 0B. PM1PM2PP2PP3_ModeratePP5_Very_Strong

The ENST00000423572.7(SCN5A):c.5347G>A(p.Glu1783Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1783Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SCN5A
ENST00000423572.7 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:24O:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

SCN5A (HGNC:10593): (sodium voltage-gated channel alpha subunit 5) The protein encoded by this gene is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram. Defects in this gene have been associated with long QT syndrome type 3 (LQT3), atrial fibrillation, cardiomyopathy, and Brugada syndrome 1, all autosomal dominant cardiac diseases. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, May 2022]

SCN5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 15 ACMG points.

PM1

In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 11 uncertain in ENST00000423572.7

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SCN5A. . Gene score misZ 2.7504 (greater than the threshold 3.09). Trascript score misZ 4.8279 (greater than threshold 3.09). GenCC has associacion of gene with progressive familial heart block, type 1A, Brugada syndrome, familial sick sinus syndrome, short QT syndrome, paroxysmal familial ventricular fibrillation, progressive familial heart block, long QT syndrome 3, familial atrial fibrillation, catecholaminergic polymorphic ventricular tachycardia, dilated cardiomyopathy, dilated cardiomyopathy 1E, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome 1, atrial standstill, familial isolated dilated cardiomyopathy, familial long QT syndrome, sick sinus syndrome 1.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

PP5

Variant 3-38551022-C-T is Pathogenic according to our data. Variant chr3-38551022-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 9377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-38551022-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN5A	NM_001099404.2 linkuse as main transcript	c.5350G>A	p.Glu1784Lys	missense_variant	28/28	ENST00000413689.6	NP_001092874.1
SCN5A	NM_000335.5 linkuse as main transcript	c.5347G>A	p.Glu1783Lys	missense_variant	28/28	ENST00000423572.7	NP_000326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN5A	ENST00000413689.6 linkuse as main transcript	c.5350G>A	p.Glu1784Lys	missense_variant	28/28	5	NM_001099404.2	ENSP00000410257	P4
SCN5A	ENST00000423572.7 linkuse as main transcript	c.5347G>A	p.Glu1783Lys	missense_variant	28/28	1	NM_000335.5	ENSP00000398266	A1	Q14524-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:24Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:9

Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2021	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Functional studies have shown that E1784K results in SCN5A channel dysfunction by causing a persistent inward sodium current and a negative shift in steady-state inactivation (Wei et al., 1999; Deschenes et al., 2000; Makita et al., 2008; Abdelsayed et al., 2018); This variant is associated with the following publications: (PMID: 10727653, 18451998, 15840476, 31737537, 10377081, 24784157, 26131924, 21321465, 26831253, 27381756, 27677334, 28341781, 28412158, 28781849, 24871449, 10973849, 10961955, 19716085, 30364184, 29483621, 24762805, 19841300, 12877697, 16379539, 18452873, 23631430, 18508782, 30530868, 28976236, 28734073, 30662450, 31484910, 30193851, 32161207, 31447099, 32383558, 33131149) -
Pathogenic, no assertion criteria provided	clinical testing	Stanford Center for Inherited Cardiovascular Disease, Stanford University	May 26, 2015	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Glu1784Lys (c.5350G>A) in SCN5A (NM_001099404.1, ENST00000413689) Given the very strong case data, segregation data, and absence in individuals unselected for rare cardiac disease, we consider this variant very likely disease causing and we do feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has been seen in at least 30 unrelated cases of inherited channelopathy, and likely more than 52 cases (not including this patient's family). There is strong segregation data. Of note, the variant has been reported with a range of SCN5A-associated phenotypes including long QT syndrome type 3, Brugada syndrome, and conduction system disease (see Makita et al 2008 for multicenter data on the varied phenotype). Interestingly, the variant appears to be the most frequently identified long QT type 3 variant and the most frequently identified Brugada syndrome variant in a variety of cohorts. Makita et al (2008) report on 44 carriers of this variant across 15 families from multiple centers around the world (many likely overlap with prior reports). Most carriers had evidence of LQT3 (93%), 22% had evidence of Brugada syndrome, and 39% had sinus node dysfunction. All of the patients with evidence of Brugada also had evidence of long QT type 3. Half of the patients with Brugada had sinus node dysfunction. Only 2/44 carriers had no evidence of these three phenotypes, indicating high penetrance in this cohort. Of note, some carriers had evidence of all three phenotypes. Wei et al (1999) reported the variant in a Caucasian family with evidence of long QT syndrome (QTc 464-527 ms in affected relatives), sudden death at 13yo while at rest with native autopsy, sinus bradycardia, prominent unit(s) waves, ventricular ectopy during bradycardic episodes with occasional sinus pauses and one family member with "isoelectric ST segments". The authors are from Vanderbilt. They sequenced select exons of SCN5A in the family. The variant segregated with disease in 4 affected family members, including two first cousins. Priori et al (2000) reported on family with long QT syndrome and this variant. It isn't completely clear from the report, but it appears that three affected members of this family had this variant (QTc 496, 510, 520). A 12yo girl in this family had a resting QTc of 480 ms. With Flecainide provocation her QT shortened to 460 ms and ST segment elevation was provoked. Splawski et al (2000) observed the variant in 2 of 262 unrelated patients with long QT who underwent analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2. Patients were ascertained in Europe and North America (may overlap with reports by Priori's group, the US long QT registry, the international long QT registry). No ancestry, segregation, or individual phenotype data was provided. (Splawski et al 2000). Priori et al (2002) observed this variant in at least one patient with Brugada syndrome from a cohort of 130 unrelated patients with Brugada, presumably recruited in Italy (though that is not clear). Ackerman's group reported 3 unrelated patients with long QT syndrome and this variant Nemec et al 2003). They do not state where subjects were recruited, but all authors are form Mayo so presumably there. It appears that sequencing was done in Ackerman's research lab at Mayo. They note that one patient with this variant had microvoltage T wave alternans at baseline. In a subsequent paper they report an additional case, for a total of 4 (Tester et al 2005). Shim et al (2005) reported on a variant, E1783K, that appears to be the same variant, but with a slightly different number system. They observed it in two infants who underwent genetic test -
Pathogenic, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2019	- -
Pathogenic, criteria provided, single submitter	clinical testing	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	Oct 23, 2020	- -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 28, 2024	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1784 of the SCN5A protein (p.Glu1784Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with long QT syndrome, sick sinus syndrome, and/or Brugada syndrome (PMID: 10377081, 10727653, 10961955, 10973849, 12877697, 16379539, 18451998, 18452873, 19841300, 21321465, 23631430, 24762805). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9377). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 32533946) did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN5A function. Experimental studies have shown that this missense change affects SCN5A function (PMID: 10377081, 10727653, 18451998). For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 26, 2017	- -

Long QT syndrome 3

Pathogenic:5

Pathogenic, criteria provided, single submitter	clinical testing	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	Jul 17, 2023	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are both known mechanisms of disease in this gene. Loss of function is usually associated with Brugada syndrome 1 (MIM#601144) and sick sinus syndrome 1 (SSS) (MIM#608567), whereas gain of function is usually associated with long QT syndrome 3 (LQTS) (MIM#603830). Dilated cardiomyopathy 1E (DCM) (MIM#601154) can be caused by variants with either a loss of function or gain of function mechanism (PMID: 29798782). (I) 0108 - This gene is associated with both recessive and dominant disease. Most conditions associated with this gene are dominantly inherited; however, SSS is caused by biallelic variants (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamic acid to lysine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (3 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0710 - Other missense variants comparable to the one identified in this case has inconclusive previous evidence for pathogenicity. The p.(Glu1783Gln) and p.(Glu1783Asp) variants have each been classified once as a VUS (ClinVar). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic by multiple clinical diagnostic laboratories and is a well-reported variant associated with Brugada syndrome and Long QT syndrome type 3 (ClinVar, PMID: 27381756). This variant has also been reported as pathogenic by VCGS in three individuals with LQTS and in one individual with a personal history of syncope and a family history of sudden cardiac death. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Pathogenic, criteria provided, single submitter	clinical testing	Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	May 28, 2020	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jun 01, 2008	- -
Likely pathogenic, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	Oct 15, 2018	This variant is interpreted as Likely Pathogenic, for Long QT syndrome 3, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. -
Pathogenic, no assertion criteria provided	research	Division of Human Genetics, Children's Hospital of Philadelphia	Feb 25, 2016	- -

Brugada syndrome

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	Blueprint Genetics	Jul 22, 2015	- -
Pathogenic, criteria provided, single submitter	clinical testing	Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	Jan 14, 2022	- -

Congenital long QT syndrome;C1142166:Brugada syndrome

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jul 08, 2016

The p.Glu1784Lys variant in SCN5A has been previously reported in >20 individual s with prolonged QT intervals, Long QT syndrome (LQTS), and/or Brugada syndrome , including 1 de novo occurrence (Wei 1999, Makita 2008, Deschenes 2000, Nakajim a 2011, Takahashi 2014). Furthermore, the variant segregated with disease in man y affected relatives (LQTS, Brugada syndrome, or prolonged QT intervals; Makita 2008, Wei 1999, Deschenes 2000, Shim 2005, Veltmann 2016). This variant has also been classified by other clinical laboratories as pathogenic in ClinVar (Variat ion ID: 9377) and has been identified in 1/111718 of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). In vitr o functional studies provide some evidence that the p.Glu1784Lys variant may imp act protein function (Deschenes 2000, Makita 2008). In summary, this variant mee ts criteria to be classified as pathogenic for LQTS and Brugada syndrome in an a utosomal dominant manner based upon presence in multiple affected individuals, s egregation studies, very low frequency in controls and functional studies. ACMG/ AMP criteria applied: PS4_Strong; PP1_Strong; PS3_Supporting, PM2. -

Long QT syndrome 1

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

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

May 10, 2016

Variant summary: The SCN5A c.5350G>A (p.Glu1784Lys) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a damaging outcome (SNPs&GO not captured due to low reliability index). This variant is absent in 121222 control chromosomes, but has been reported in the literature in numerous affected individuals, including patients with both LQTS and Brugada syndrome. In functional studies, the variant showed a persistent inward sodium current, which has also been previously observed as a functional defect in other LQTS SCN5A mutations (Wei_1999, Deschenes_2000). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. -

Brugada syndrome 1

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

SCN5A-related disorder

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

DASA

Jan 05, 2022

The c.5350G>A;p.(Glu1784Lys) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 9377; OMIM: 600163.0008; PMID: 18451998; 10377081; 24762805; 10727653; 21321465; 19841300; 12877697; 10973849) - PS4. Well-established in vitro or in vivo functional studies support a damaging effect on the gene or gene product (PMID: 10377081, 10727653, 18451998) - PS3_moderate. The variant is present at low allele frequencies population databases (rs137854601– gnomAD 0.0001973%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The variant co-segregated with disease in multiple affected family members (PMID: 18451998; 10377081; 24762805) - PP1. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. -

Sinoatrial node disorder

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

SUDDEN INFANT DEATH SYNDROME;C1832680:Dilated cardiomyopathy 1E;C1837845:Sick sinus syndrome 1;C1859062:Long QT syndrome 3;C1879286:Progressive familial heart block, type 1A;C2751898:Ventricular fibrillation, paroxysmal familial, type 1;C3151464:Atrial fibrillation, familial, 10;C4551804:Brugada syndrome 1

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

PM2_Supporting+PS4+PP4+PP1_Moderate+PS3_Moderate -

Cardiovascular phenotype

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The p.E1784K pathogenic mutation (also known as c.5350G>A), located in coding exon 27 of the SCN5A gene, results from a G to A substitution at nucleotide position 5350. The glutamic acid at codon 1784 is replaced by lysine, an amino acid with some similar properties. The first report of this mutation involved a family with a clinical diagnosis of autosomal dominant long QT syndrome (LQTS), in which the mutation was confirmed to co-segregrate in all affected, but none of the unaffected, family members. Functional analysis revealed a negative shift of steady-state sodium channel activation, thus suggesting delayed cardiac repolarization (Wei et al. Circulation. 1999:99(24):3165-71). Additional functional analysis revealed p.E1784K induced persistent inward sodium current activity with a faster recovery from the inactivation state suggesting an unstable inactivation state overall (Deschenes et al. Cardiovasc Res. 2000;46(1):55-65). There are reports of mixed clinical phenotypes involving LQTS, Brugada syndrome (BrS), and sinus node dysfunction among individuals with the p.E1784K mutation (Makita et al. J Clin Invest. 2008;118(6):2219-29; Sandhu A et al. Clin Case Rep 2017 Aug;5(8):1315-1319). This is considered the most common SCN5A mutation, and most recently demonstrated segregation in a family with BrS, LQTS, and cardiac conduction disease (CCD) (Veltmann C et al. J Am Heart Assoc. 2016;5(7):e003379). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. -

Cardiac arrhythmia

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Sep 01, 2023

This missense variant replaces glutamate with lysine at codon 1784 of the SCN5A protein. This variant is found within the highly conserved C-terminal region (a.a. 1773-2016). Rare nontruncating variants in this region have been shown to be significantly overrepresented in individuals with Brugada syndrome or Long QT syndrome (PMID: 32893267). Functional studies have shown that this variant causes a reduction in peak sodium currents, a negative shift of steady-state inactivation, and an increase in late sodium currents in transfected cells (PMID: 18451998, 24439875, 27381756). This variant has been reported in over two hundred individuals affected with Brugada syndrome, long QT syndrome, sinus node dysfunction, or cardiac conduction disease from various population (PMID: 10377081, 18451998, 20129283, 21321465, 27381756, 27566755, 33164571). This variant has been shown to segregate with disease in multiple families (PMID: 10377081, 18451998, 27381756). Some carriers have exhibited phenotypic characteristics of both Brugada syndrome and long QT syndrome (PMID: 18451998, 21321465, 27381756, 28781849). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -

Congenital long QT syndrome

Other:1

not provided, no classification provided

literature only

Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust

This variant has been reported as associated with Long QT syndrome in the following publications (PMID:10377081;PMID:10961955;PMID:10973849;PMID:12877697;PMID:15840476;PMID:16379539;PMID:18451998;PMID:19716085;PMID:19841300;PMID:10727653). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

CardioboostCm

Uncertain

0.59

BayesDel_addAF

Pathogenic

0.49

BayesDel_noAF

Pathogenic

0.47

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.70

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

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

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

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.93

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

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.1

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

MutationTaster

Benign

1.0

A;A;A;A;A;A;A;A;A;A

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.6

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

REVEL

Pathogenic

0.91

Sift

Uncertain

0.0010

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

Sift4G

Benign

0.15

T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;D;.;D;.;P;D;.;.

Vest4

0.80

MutPred

0.76

.;.;Gain of ubiquitination at E1784 (P = 0.0016);.;.;Gain of ubiquitination at E1784 (P = 0.0016);.;.;.;

MVP

0.96

MPC

1.5

ClinPred

0.99

GERP RS

4.8

Varity_R

0.86

gMVP

0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over