NM_003098.3(SNTA1):c.787G>T (p.Ala263Ser) AND Congenital long QT syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Aug 8, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000266318.7

Allele description [Variation Report for NM_003098.3(SNTA1):c.787G>T (p.Ala263Ser)]

NM_003098.3(SNTA1):c.787G>T (p.Ala263Ser)

Gene:

SNTA1:syntrophin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.21

Genomic location:

Preferred name:

NM_003098.3(SNTA1):c.787G>T (p.Ala263Ser)

Other names:

p.A263S:GCC>TCC; p.Ala263Ser

HGVS:

NC_000020.11:g.33412697C>A
NG_011622.1:g.36196G>T
NM_003098.3:c.787G>TMANE SELECT
NP_003089.1:p.Ala263Ser
NP_003089.1:p.Ala263Ser
LRG_332t1:c.787G>T
LRG_332:g.36196G>T
LRG_332p1:p.Ala263Ser
NC_000020.10:g.32000503C>A
NM_003098.2:c.787G>T

Protein change:

A263S

Links:

dbSNP: rs150576530

NCBI 1000 Genomes Browser:

rs150576530

Molecular consequence:

NM_003098.3:c.787G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital long QT syndrome (RWS)
Synonyms:: Familial long QT syndrome; Romano-Ward syndrome; Ventricular fibrillation with prolonged QT interval
Identifiers:: MONDO: MONDO:0019171; MedGen: C1141890; Orphanet: 768; OMIM: PS192500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000433505	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Uncertain significance (Jun 14, 2016)	germline	clinical testing	ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV004175715	Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 8, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28837624, 23861362, 32893267, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000433505

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification 20161018)

Uncertain significance
(Jun 14, 2016)

germline

clinical testing

ICSL_Variant_Classification_20161018.pdf,

Citation Link,

SCV004175715

Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Aug 8, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
Caucasian	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rare variants in genes encoding the cardiac sodium channel and associated compounds and their impact on outcome of catheter ablation of atrial fibrillation.

Husser D, Ueberham L, Hindricks G, Büttner P, Ingram C, Weeke P, Shoemaker MB, Adams V, Arya A, Sommer P, Darbar D, Roden DM, Bollmann A.

PLoS One. 2017;12(8):e0183690. doi: 10.1371/journal.pone.0183690.

PubMed [citation]

PMID:: 28837624
PMCID:: PMC5570360

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

See all PubMed Citations (4)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000433505.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations, SCV004175715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	Caucasian	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Heterozygous variant NM_003098:c.787G>T (p.Ala263Ser) in the SNTA1 gene was found on WES data in female proband (13 y.o., Caucasian) with Long QT syndrome. An additional variant NM_000238:c.2653C>T (p.Arg885Cys) in the KCNH2 gene was found in this proband. This variant is in The Genome Aggregation Database (gnomAD) v2.1.1 with total MAF 0.0004748 (Date of access 08-08-2023). Clinvar contains entry for this variant (Variation ID: 190914). This variant has been reported in 2 studies in patients with variable phenotypes (PMID: 28837624, 23861362). Most in silico predictors show benign result of the protein change (varsome.com). In accordance with ACMG(2015) criteria and enhanced rare variant interpretation in inherited arrhythmias (PMID: 32893267) this variant is classified as Likely benign with following criteria selected: BS1, BP4.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

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