NM_002234.4(KCNA5):c.1540G>A (p.Val514Ile) AND Atrial fibrillation, familial, 7

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 25, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001997462.4

Allele description [Variation Report for NM_002234.4(KCNA5):c.1540G>A (p.Val514Ile)]

NM_002234.4(KCNA5):c.1540G>A (p.Val514Ile)

Gene:

KCNA5:potassium voltage-gated channel subfamily A member 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.32

Genomic location:

Preferred name:

NM_002234.4(KCNA5):c.1540G>A (p.Val514Ile)

HGVS:

NC_000012.12:g.5045687G>A
NG_012198.1:g.6769G>A
NM_002234.4:c.1540G>AMANE SELECT
NP_002225.2:p.Val514Ile
NC_000012.11:g.5154853G>A

Protein change:

V514I

Links:

dbSNP: rs1172712297

NCBI 1000 Genomes Browser:

rs1172712297

Molecular consequence:

NM_002234.4:c.1540G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrial fibrillation, familial, 7 (ATFB7)
Identifiers:: MONDO: MONDO:0012828; MedGen: C2677106; OMIM: 612240

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002230212	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19029374, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002230212

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 2021)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Kv channel gating requires a compatible S4-S5 linker and bottom part of S6, constrained by non-interacting residues.

Labro AJ, Raes AL, Grottesi A, Van Hoorick D, Sansom MS, Snyders DJ.

J Gen Physiol. 2008 Dec;132(6):667-80. doi: 10.1085/jgp.200810048.

PubMed [citation]

PMID:: 19029374
PMCID:: PMC2585865

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002230212.3

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

Description

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. Experimental studies have shown that this missense change affects KCNA5 function (PMID: 19029374). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with KCNA5-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 514 of the KCNA5 protein (p.Val514Ile).

#	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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