ClinVar Miner

Submissions for variant NM_133497.4(KCNV2):c.1381G>T (p.Gly461Ter)

dbSNP: rs149648640
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001932525 SCV002133789 pathogenic not provided 2023-04-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the KCNV2 protein in which other variant(s) (p.Leu469Trpfs*35) have been determined to be pathogenic (PMID: 18400204). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1367585). This premature translational stop signal has been observed in individual(s) with retinal cone dystrophy (PMID: 19952985). This variant is present in population databases (rs149648640, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Gly461*) in the KCNV2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acid(s) of the KCNV2 protein.
PreventionGenetics, part of Exact Sciences RCV003407863 SCV004107854 likely pathogenic KCNV2-related disorder 2023-05-29 criteria provided, single submitter clinical testing The KCNV2 c.1381G>T variant is predicted to result in premature protein termination (p.Gly461*). This variant has been reported along with a second KCNV2 variant in an individual with cone dystrophy (Robson et al. 2009. PubMed ID: 19952985). This variant is reported in 0.0085% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-2729470-G-T). Nonsense variants in KCNV2 are expected to be pathogenic. Given the evidence, we interpret c.1381G>T (p.Gly461*) as likely pathogenic.
GeneDx RCV001932525 SCV004170316 uncertain significance not provided 2023-04-04 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation, as the last 85 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD.; This variant is associated with the following publications: (PMID: 19952985)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004815691 SCV005072693 pathogenic Retinal dystrophy 2020-01-01 criteria provided, single submitter clinical testing

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