ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.1130C>T (p.Thr377Met)

dbSNP: rs1571636501
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Taipei Veterans General Hospital, Neurological Institute RCV000853621 SCV000899234 pathogenic Spinocerebellar ataxia type 19/22 2019-04-20 criteria provided, single submitter clinical testing SCA19/22-associated mutation
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000853621 SCV001430002 pathogenic Spinocerebellar ataxia type 19/22 2020-02-28 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268117 SCV001446777 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000853621 SCV002512703 pathogenic Spinocerebellar ataxia type 19/22 2021-07-05 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 moderate, PM2 moderate, PP1 strong, PP2 supporting, PP3 supporting
Athena Diagnostics RCV001268117 SCV002770819 pathogenic not provided 2023-04-25 criteria provided, single submitter clinical testing This variant appears to segregate with disease in at least one family. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. In experimental assays, this variant was found to reduce potassium channel current and alter membrane potential, as well as reduce protein half-life and impair surface expression in cells (PMID: 31293010).
Labcorp Genetics (formerly Invitae), Labcorp RCV000853621 SCV003275863 pathogenic Spinocerebellar ataxia type 19/22 2022-01-03 criteria provided, single submitter clinical testing This missense change has been observed in individuals with spinocerebellar ataxia (PMID: 23280837, 29527639). It has also been observed to segregate with disease in related individuals. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects KCND3 function (PMID: 31293010). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 626319). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 377 of the KCND3 protein (p.Thr377Met).

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