NM_002234.4(KCNA5):c.196C>T (p.Pro66Ser) AND Atrial fibrillation, familial, 7

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 22, 2023
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:: RCV000824001.10

Allele description [Variation Report for NM_002234.4(KCNA5):c.196C>T (p.Pro66Ser)]

NM_002234.4(KCNA5):c.196C>T (p.Pro66Ser)

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.196C>T (p.Pro66Ser)

HGVS:

NC_000012.12:g.5044343C>T
NG_012198.1:g.5425C>T
NM_002234.4:c.196C>TMANE SELECT
NP_002225.2:p.Pro66Ser
NC_000012.11:g.5153509C>T
NM_002234.2:c.196C>T

Protein change:

P66S

Links:

dbSNP: rs368699451

NCBI 1000 Genomes Browser:

rs368699451

Molecular consequence:

NM_002234.4:c.196C>T - 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
SCV000964876	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32508047, 28492532
SCV002816059	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 20, 2021)	unknown	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

SCV000964876

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 22, 2023)

germline

clinical testing

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

SCV002816059

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Aug 20, 2021)

unknown

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

Citations

PubMed

Identification of potential candidate genes and pathways in atrioventricular nodal reentry tachycardia by whole-exome sequencing.

Luo R, Zheng C, Yang H, Chen X, Jiang P, Wu X, Yang Z, Shen X, Li X.

Clin Transl Med. 2020 Jan;10(1):238-257. doi: 10.1002/ctm2.25. Erratum in: Clin Transl Med. 2021 Feb;11(2):e274. doi: 10.1002/ctm2.274.

PubMed [citation]

PMID:: 32508047
PMCID:: PMC7240861

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000964876.6

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

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 66 of the KCNA5 protein (p.Pro66Ser). This variant is present in population databases (rs368699451, gnomAD 0.02%). This missense change has been observed in individual(s) with atrioventricular nodal reentry tachycardia (PMID: 32508047). ClinVar contains an entry for this variant (Variation ID: 665674). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 Fulgent Genetics, Fulgent Genetics, SCV002816059.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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