NM_000335.5(SCN5A):c.1914C>T (p.Gly638=) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jan 22, 2024
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:: RCV000489418.18

Allele description [Variation Report for NM_000335.5(SCN5A):c.1914C>T (p.Gly638=)]

NM_000335.5(SCN5A):c.1914C>T (p.Gly638=)

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.1914C>T (p.Gly638=)

HGVS:

NC_000003.12:g.38599027G>A
NG_008934.1:g.55646C>T
NM_000335.5:c.1914C>TMANE SELECT
NM_001099404.2:c.1914C>T
NM_001099405.2:c.1914C>T
NM_001160160.2:c.1914C>T
NM_001160161.2:c.1914C>T
NM_001354701.2:c.1914C>T
NM_198056.3:c.1914C>T
NP_000326.2:p.Gly638=
NP_001092874.1:p.Gly638=
NP_001092875.1:p.Gly638=
NP_001153632.1:p.Gly638=
NP_001153633.1:p.Gly638=
NP_001341630.1:p.Gly638=
NP_932173.1:p.Gly638=
NP_932173.1:p.Gly638=
LRG_289t1:c.1914C>T
LRG_289:g.55646C>T
LRG_289p1:p.Gly638=
NC_000003.11:g.38640518G>A
NM_198056.2:c.1914C>T

Links:

dbSNP: rs764488677

NCBI 1000 Genomes Browser:

rs764488677

Molecular consequence:

NM_000335.5:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099404.2:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001099405.2:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160160.2:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001160161.2:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001354701.2:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]
NM_198056.3:c.1914C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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RecName: Full=Ras association domain-containing protein 1
RecName: Full=Ras association domain-containing protein 1
gi|50401686|sp|Q9NS23.1|RASF1_HUMAN

Protein
MFS transporter [Methanocella arvoryzae]
MFS transporter [Methanocella arvoryzae]
gi|500975464|ref|WP_012037211.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000576621	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Apr 25, 2017)	germline	clinical testing	Citation Link,
SCV000827856	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004702731	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jan 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000576621

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Apr 25, 2017)

germline

clinical testing

Citation Link,

SCV000827856

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 22, 2024)

germline

clinical testing

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

SCV004702731

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely benign
(Jan 1, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000576621.3

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

Description

The c.1914 C>T (G638G) variant of uncertain significance in the SCN5A gene has not been published as pathogenic or been reported as benign to our knowledge. At the protein level, the c.1914 C>T (G638G) variant results in a synonymous amino acid substitution in the glycine 638 residue. At the nucleotide level, this substitution occurs at a nucleotide position that is not conserved, where thymine is the native nucleotide in multiple species. In silico splicing algorithms predict this variant results in the creation of a cryptic splice donor site upstream of the natural donor site in intron 13 of the SCN5A gene; however, in the absence of functional mRNA studies, the physiological consequence of this variant on splicing cannot be precisely determined. Multiple other splice site variants in the SCN5A gene have been reported in the Human Genome Mutation Database in association with arrhythmia (Stenson et al., 2014). Furthermore, the c.1914 C>T (G638G) variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000827856.3

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV004702731.7

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

Description

SCN5A: BP4, BP7

#	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		1	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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