ClinVar Miner

Submissions for variant NM_012281.3(KCND2):c.1210G>A (p.Val404Met)

dbSNP: rs587777631
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001224876 SCV001397102 pathogenic Early myoclonic encephalopathy 2020-02-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect KCND2 protein function (PMID: 29581270). This variant has been observed to be de novo in a family affected with seizures, autism and language delay (PMID: 24501278, Invitae). ClinVar contains an entry for this variant (Variation ID: 144007). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 404 of the KCND2 protein (p.Val404Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine.
Ambry Genetics RCV003298146 SCV004001714 pathogenic Inborn genetic diseases 2023-05-30 criteria provided, single submitter clinical testing The c.1210G>A (p.V404M) alteration is located in exon 2 (coding exon 2) of the KCND2 gene. This alteration results from a G to A substitution at nucleotide position 1210, causing the valine (V) at amino acid position 404 to be replaced by a methionine (M). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was reported as de novo in multiple unrelated individuals with KCND2-related neurodevelopmental disorder (Lee, 2014; Zhang, 2021). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Overall, functional studies show aberrant channel activity in vitro (Lee, 2014; Lin, 2018; Zhang, 2021; Bavan, 2022). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.
OMIM RCV000133516 SCV000188591 uncertain significance not provided 2014-07-01 no assertion criteria provided literature only

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