NM_002234.4(KCNA5):c.106T>A (p.Cys36Ser) AND Atrial fibrillation, familial, 7

Clinical significance:Uncertain significance (Last evaluated: Jan 31, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000686772.3

Allele description [Variation Report for NM_002234.4(KCNA5):c.106T>A (p.Cys36Ser)]

NM_002234.4(KCNA5):c.106T>A (p.Cys36Ser)

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.106T>A (p.Cys36Ser)
HGVS:
  • NC_000012.12:g.5044253T>A
  • NG_012198.1:g.5335T>A
  • NM_002234.4:c.106T>AMANE SELECT
  • NP_002225.2:p.Cys36Ser
  • NC_000012.11:g.5153419T>A
  • NM_002234.3:c.106T>A
Protein change:
C36S
Links:
dbSNP: rs910072879
NCBI 1000 Genomes Browser:
rs910072879
Molecular consequence:
  • NM_002234.4:c.106T>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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000814305Invitaecriteria provided, single submitter
Uncertain significance
(Jan 31, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000814305.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces cysteine with serine at codon 36 of the KCNA5 protein (p.Cys36Ser). The cysteine residue is weakly conserved and there is a moderate physicochemical difference between cysteine and serine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNA5-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 8, 2022

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