NM_000335.5(SCN5A):c.560C>G (p.Thr187Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 6, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003139965.6

Allele description [Variation Report for NM_000335.5(SCN5A):c.560C>G (p.Thr187Ser)]

NM_000335.5(SCN5A):c.560C>G (p.Thr187Ser)

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.560C>G (p.Thr187Ser)

HGVS:

NC_000003.12:g.38620894G>C
NG_008934.1:g.33779C>G
NM_000335.5:c.560C>GMANE SELECT
NM_001099404.2:c.560C>G
NM_001099405.2:c.560C>G
NM_001160160.2:c.560C>G
NM_001160161.2:c.560C>G
NM_001354701.2:c.560C>G
NM_198056.3:c.560C>G
NP_000326.2:p.Thr187Ser
NP_001092874.1:p.Thr187Ser
NP_001092875.1:p.Thr187Ser
NP_001153632.1:p.Thr187Ser
NP_001153633.1:p.Thr187Ser
NP_001341630.1:p.Thr187Ser
NP_932173.1:p.Thr187Ser
NP_932173.1:p.Thr187Ser
LRG_289t1:c.560C>G
LRG_289:g.33779C>G
LRG_289p1:p.Thr187Ser
NC_000003.11:g.38662385G>C
NM_198056.2:c.560C>G

Protein change:

T187S

Links:

dbSNP: rs199473558

NCBI 1000 Genomes Browser:

rs199473558

Molecular consequence:

NM_000335.5:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.560C>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000760283	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 6, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 30193851, 16325048, 20539757, 25348405, 28492532
SCV003821331	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 9, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000760283

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 6, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003821331

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 9, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Clinical presentation and follow-up of women affected by Brugada syndrome.

Berthome P, Tixier R, Briand J, Geoffroy O, Babuty D, Mansourati J, Jesel L, Dupuis JM, Bru P, Kyndt F, Guyomarch B, Thollet A, Behar N, Mabo P, Sacher F, Probst V, Gourraud JB.

Heart Rhythm. 2019 Feb;16(2):260-267. doi: 10.1016/j.hrthm.2018.08.032. Epub 2018 Sep 5.

PubMed [citation]

PMID:: 30193851

High risk for bradyarrhythmic complications in patients with Brugada syndrome caused by SCN5A gene mutations.

Makiyama T, Akao M, Tsuji K, Doi T, Ohno S, Takenaka K, Kobori A, Ninomiya T, Yoshida H, Takano M, Makita N, Yanagisawa F, Higashi Y, Takeyama Y, Kita T, Horie M.

J Am Coll Cardiol. 2005 Dec 6;46(11):2100-6. Epub 2005 Nov 4.

PubMed [citation]

PMID:: 16325048

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000760283.3

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

Description

This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 187 of the SCN5A protein (p.Thr187Ser). This variant is present in population databases (rs199473558, gnomAD 0.009%). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 30193851; Invitae). ClinVar contains an entry for this variant (Variation ID: 532122). 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 tolerated. This variant disrupts the p.Thr187 amino acid residue in SCN5A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16325048, 20539757, 25348405). 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

From Revvity Omics, Revvity, SCV003821331.2

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

#	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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