NM_000335.5(SCN5A):c.2822C>T (p.Ser941Phe) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 17, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003734579.2

Allele description [Variation Report for NM_000335.5(SCN5A):c.2822C>T (p.Ser941Phe)]

NM_000335.5(SCN5A):c.2822C>T (p.Ser941Phe)

Genes:

LOC110121269:VISTA enhancer hs2177 [Gene]
SCN5A:sodium voltage-gated channel alpha subunit 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000335.5(SCN5A):c.2822C>T (p.Ser941Phe)

HGVS:

NC_000003.12:g.38581337G>A
NG_008934.1:g.73336C>T
NG_053884.1:g.3076G>A
NM_000335.5:c.2822C>TMANE SELECT
NM_001099404.2:c.2822C>T
NM_001099405.2:c.2822C>T
NM_001160160.2:c.2822C>T
NM_001160161.2:c.2822C>T
NM_001354701.2:c.2822C>T
NM_198056.3:c.2822C>T
NP_000326.2:p.Ser941Phe
NP_000326.2:p.Ser941Phe
NP_001092874.1:p.Ser941Phe
NP_001092874.1:p.Ser941Phe
NP_001092875.1:p.Ser941Phe
NP_001153632.1:p.Ser941Phe
NP_001153633.1:p.Ser941Phe
NP_001341630.1:p.Ser941Phe
NP_932173.1:p.Ser941Phe
NP_932173.1:p.Ser941Phe
LRG_289t1:c.2822C>T
LRG_289t2:c.2822C>T
LRG_289t3:c.2822C>T
LRG_289:g.73336C>T
LRG_289p1:p.Ser941Phe
LRG_289p2:p.Ser941Phe
LRG_289p3:p.Ser941Phe
NC_000003.11:g.38622828G>A
NM_000335.4:c.2822C>T
NM_001099404.1:c.2822C>T
NM_198056.2:c.2822C>T
NR_176299.1:n.3568C>T

Protein change:

S941F

Molecular consequence:

NM_000335.5:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.2822C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_176299.1:n.3568C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004540360	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 17, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30059973, 10911008, 17698727, 20339117, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004540360

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 17, 2023)

germline

clinical testing

PubMed (5)
[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

Citations

PubMed

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Baruteau AE, Kyndt F, Behr ER, Vink AS, Lachaud M, Joong A, Schott JJ, Horie M, Denjoy I, Crotti L, Shimizu W, Bos JM, Stephenson EA, Wong L, Abrams DJ, Davis AM, Winbo A, Dubin AM, Sanatani S, Liberman L, Kaski JP, Rudic B, et al.

Eur Heart J. 2018 Aug 14;39(31):2879-2887. doi: 10.1093/eurheartj/ehy412.

PubMed [citation]

PMID:: 30059973

A molecular link between the sudden infant death syndrome and the long-QT syndrome.

Schwartz PJ, Priori SG, Dumaine R, Napolitano C, Antzelevitch C, Stramba-Badiale M, Richard TA, Berti MR, Bloise R.

N Engl J Med. 2000 Jul 27;343(4):262-7. No abstract available.

PubMed [citation]

PMID:: 10911008

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004540360.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense change has been observed in individual(s) with SCN5A-related conditions (PMID: 30059973). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 941 of the SCN5A protein (p.Ser941Phe). This variant is not present in population databases (gnomAD no frequency). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Ser941 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10911008, 17698727, 20339117). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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

Last Updated: Sep 29, 2024

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