NM_000335.5(SCN5A):c.4913G>A (p.Gly1638Glu) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 2, 2024
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:: RCV001550047.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.4913G>A (p.Gly1638Glu)]

NM_000335.5(SCN5A):c.4913G>A (p.Gly1638Glu)

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.4913G>A (p.Gly1638Glu)

HGVS:

NC_000003.12:g.38551456C>T
NG_008934.1:g.103217G>A
NM_000335.5:c.4913G>AMANE SELECT
NM_001099404.2:c.4916G>A
NM_001099405.2:c.4862G>A
NM_001160160.2:c.4817G>A
NM_001160161.2:c.4754G>A
NM_001354701.2:c.4859G>A
NM_198056.3:c.4916G>A
NP_000326.2:p.Gly1638Glu
NP_001092874.1:p.Gly1639Glu
NP_001092875.1:p.Gly1621Glu
NP_001153632.1:p.Gly1606Glu
NP_001153633.1:p.Gly1585Glu
NP_001341630.1:p.Gly1620Glu
NP_932173.1:p.Gly1639Glu
LRG_289t1:c.4916G>A
LRG_289:g.103217G>A
NC_000003.11:g.38592947C>T
NM_198056.2:c.4916G>A

Protein change:

G1585E

Links:

dbSNP: rs370819854

NCBI 1000 Genomes Browser:

rs370819854

Molecular consequence:

NM_000335.5:c.4913G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.4916G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.4862G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.4817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.4754G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.4859G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.4916G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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RecName: Full=Prostaglandin F2 receptor negative regulator; AltName: Full=CD9 pa...
RecName: Full=Prostaglandin F2 receptor negative regulator; AltName: Full=CD9 partner 1; Short=CD9P-1; AltName: Full=Glu-Trp-Ile EWI motif-containing protein F; Short=EWI-F; AltName: Full=Prostaglandin F2-alpha receptor regulatory protein; AltName: Full=Prostaglandin F2-alpha receptor-associated protein; AltName: CD_antigen=CD315; Flags: Precursor
gi|28201801|sp|Q9P2B2.2|FPRP_HUMAN

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001770317	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 2, 2024)	germline	clinical testing	Citation Link,
SCV002156571	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 16, 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

SCV001770317

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Apr 2, 2024)

germline

clinical testing

Citation Link,

SCV002156571

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 16, 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	yes	not provided	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, SCV001770317.2

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

Description

Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

#	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, SCV002156571.3

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

Description

This sequence change replaces glycine with glutamic acid at codon 1639 of the SCN5A protein (p.Gly1639Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCN5A-related conditions.

#	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: Oct 13, 2024

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