Submissions for variant NM_001378969.1(KCND3):c.1456A>G (p.Thr486Ala)

gnomAD frequency: 0.00077  dbSNP: rs149008060

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079066	SCV000559635	likely benign	Spinocerebellar ataxia type 19/22	2024-01-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000482547	SCV000565087	uncertain significance	not specified	2016-12-22	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the KCND3 gene. The T486A variant in the KCND3 has been observed in 2 unrelated individuals with early-onset atrial fibrillation and was absent from 432 control individuals (Olesen et al., 2013). Nevertheless, Giudicessi et al. (2011) observed the T486A variant in 1 ostensibly healthy control individual, and the Exome Aggregation Consortium (ExAC) data set reported T486A was observed in 44/16148 (0.27%) alleles from individuals of European background, indicating it may be a rare (benign) variant in this population. The T486A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Athena Diagnostics	RCV000482547	SCV001476503	benign	not specified	2020-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002393199	SCV002695883	likely benign	Cardiovascular phenotype	2019-02-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000786333	SCV004124214	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	KCND3: PP3, BS1
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000786333	SCV000925108	uncertain significance	not provided	2016-07-07	no assertion criteria provided	provider interpretation
PreventionGenetics, part of Exact Sciences	RCV004551555	SCV004741113	likely benign	KCND3-related disorder	2023-03-20	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).