NM_000335.5(SCN5A):c.65C>T (p.Ala22Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 10, 2022
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:: RCV000272753.6

Allele description [Variation Report for NM_000335.5(SCN5A):c.65C>T (p.Ala22Val)]

NM_000335.5(SCN5A):c.65C>T (p.Ala22Val)

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.65C>T (p.Ala22Val)

HGVS:

NC_000003.12:g.38633243G>A
NG_008934.1:g.21430C>T
NM_000335.5:c.65C>TMANE SELECT
NM_001099404.2:c.65C>T
NM_001099405.2:c.65C>T
NM_001160160.2:c.65C>T
NM_001160161.2:c.65C>T
NM_001354701.2:c.65C>T
NM_198056.3:c.65C>T
NP_000326.2:p.Ala22Val
NP_001092874.1:p.Ala22Val
NP_001092875.1:p.Ala22Val
NP_001153632.1:p.Ala22Val
NP_001153633.1:p.Ala22Val
NP_001341630.1:p.Ala22Val
NP_932173.1:p.Ala22Val
NP_932173.1:p.Ala22Val
LRG_289t1:c.65C>T
LRG_289:g.21430C>T
LRG_289p1:p.Ala22Val
NC_000003.11:g.38674734G>A
NM_198056.2:c.65C>T

Protein change:

A22V

Links:

dbSNP: rs776925980

NCBI 1000 Genomes Browser:

rs776925980

Molecular consequence:

NM_000335.5:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.65C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000332553	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jul 10, 2015)	germline	clinical testing	Citation Link,
SCV000823009	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 10, 2022)	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

SCV000332553

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Jul 10, 2015)

germline

clinical testing

Citation Link,

SCV000823009

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 10, 2022)

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	1	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 Eurofins Ntd Llc (ga), SCV000332553.4

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000823009.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 22 of the SCN5A protein (p.Ala22Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 281662). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: Nov 3, 2024

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