NM_000335.5(SCN5A):c.178G>A (p.Ala60Thr) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 11, 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:: RCV003136509.5

Allele description [Variation Report for NM_000335.5(SCN5A):c.178G>A (p.Ala60Thr)]

NM_000335.5(SCN5A):c.178G>A (p.Ala60Thr)

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.178G>A (p.Ala60Thr)

HGVS:

NC_000003.12:g.38633130C>T
NG_008934.1:g.21543G>A
NM_000335.5:c.178G>AMANE SELECT
NM_001099404.2:c.178G>A
NM_001099405.2:c.178G>A
NM_001160160.2:c.178G>A
NM_001160161.2:c.178G>A
NM_001354701.2:c.178G>A
NM_001407185.1:c.178G>A
NM_001407186.1:c.178G>A
NM_001407187.1:c.178G>A
NM_198056.3:c.178G>A
NP_000326.2:p.Ala60Thr
NP_000326.2:p.Ala60Thr
NP_001092874.1:p.Ala60Thr
NP_001092874.1:p.Ala60Thr
NP_001092875.1:p.Ala60Thr
NP_001153632.1:p.Ala60Thr
NP_001153633.1:p.Ala60Thr
NP_001341630.1:p.Ala60Thr
NP_001394114.1:p.Ala60Thr
NP_001394115.1:p.Ala60Thr
NP_001394116.1:p.Ala60Thr
NP_932173.1:p.Ala60Thr
NP_932173.1:p.Ala60Thr
LRG_289t1:c.178G>A
LRG_289t2:c.178G>A
LRG_289t3:c.178G>A
LRG_289:g.21543G>A
LRG_289p1:p.Ala60Thr
LRG_289p2:p.Ala60Thr
LRG_289p3:p.Ala60Thr
NC_000003.11:g.38674621C>T
NM_000335.4:c.178G>A
NM_001099404.1:c.178G>A
NM_198056.2:c.178G>A
NR_176299.1:n.387G>A

Protein change:

A60T

Molecular consequence:

NM_000335.5:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407185.1:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407186.1:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407187.1:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.178G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Rattus norvegicus tumor protein p53 (Tp53), transcript variant 2, mRNA
Rattus norvegicus tumor protein p53 (Tp53), transcript variant 2, mRNA
gi|2725760867|ref|NM_001429993.1|

Nucleotide
Lysidice collaris voucher USNM1122617 18S ribosomal RNA gene, partial sequence
Lysidice collaris voucher USNM1122617 18S ribosomal RNA gene, partial sequence
gi|296885154|gb|GQ497516.1|

Nucleotide
Ranunculus yunnanensis
Ranunculus yunnanensis
Ranunculus yunnanensis RefSeq Genome

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003821340	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 2, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004687924	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 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

SCV003821340

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 2, 2020)

germline

clinical testing

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

SCV004687924

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Revvity Omics, Revvity, SCV003821340.2

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004687924.1

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

Description

This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 60 of the SCN5A protein (p.Ala60Thr). 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. 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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