NM_000335.5(SCN5A):c.206G>A (p.Gly69Asp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 12, 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:: RCV003656670.3

Allele description [Variation Report for NM_000335.5(SCN5A):c.206G>A (p.Gly69Asp)]

NM_000335.5(SCN5A):c.206G>A (p.Gly69Asp)

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.206G>A (p.Gly69Asp)

Other names:

p.Gly69Asp

HGVS:

NC_000003.12:g.38633102C>T
NG_008934.1:g.21571G>A
NM_000335.5:c.206G>AMANE SELECT
NM_001099404.2:c.206G>A
NM_001099405.2:c.206G>A
NM_001160160.2:c.206G>A
NM_001160161.2:c.206G>A
NM_001354701.2:c.206G>A
NM_198056.3:c.206G>A
NP_000326.2:p.Gly69Asp
NP_001092874.1:p.Gly69Asp
NP_001092875.1:p.Gly69Asp
NP_001153632.1:p.Gly69Asp
NP_001153633.1:p.Gly69Asp
NP_001341630.1:p.Gly69Asp
NP_932173.1:p.Gly69Asp
LRG_289t1:c.206G>A
LRG_289:g.21571G>A
NC_000003.11:g.38674593C>T
NM_198056.2:c.206G>A

Protein change:

G69D

Links:

dbSNP: rs758404546

NCBI 1000 Genomes Browser:

rs758404546

Molecular consequence:

NM_000335.5:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099404.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001099405.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160160.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001160161.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354701.2:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198056.3:c.206G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001420018	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005409164	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 12, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33797273, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001420018

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 1, 2024)

germline

clinical testing

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

SCV005409164

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 12, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Single-cell transcriptomics trajectory and molecular convergence of clinically relevant mutations in Brugada syndrome.

Tambi R, Abdel Hameid R, Bankapur A, Nassir N, Begum G, Alsheikh-Ali A, Uddin M, Berdiev BK.

Am J Physiol Heart Circ Physiol. 2021 May 1;320(5):H1935-H1948. doi: 10.1152/ajpheart.00061.2021. Epub 2021 Apr 2.

PubMed [citation]

PMID:: 33797273

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001420018.4

#	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, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 69 of the SCN5A protein (p.Gly69Asp). This variant is present in population databases (rs758404546, gnomAD 0.01%). 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: 925496). 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 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

From Mayo Clinic Laboratories, Mayo Clinic, SCV005409164.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

PP3

#	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

Last Updated: Nov 30, 2024

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