ClinVar Miner

Submissions for variant NM_001367721.1(CASK):c.802T>C (p.Tyr268His)

dbSNP: rs137852817
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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 RCV002512982 SCV003445138 uncertain significance Intellectual disability, CASK-related, X-linked 2022-04-22 criteria provided, single submitter clinical testing 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. Experimental studies have shown that this missense change does not substantially affect CASK function (PMID: 23406872, 24505460, 33090494). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). ClinVar contains an entry for this variant (Variation ID: 11533). This missense change has been observed in individual(s) with CASK-related conditions (PMID: 20029458). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 268 of the CASK protein (p.Tyr268His).
GeneDx RCV003313028 SCV004012483 likely pathogenic not provided 2023-09-15 criteria provided, single submitter clinical testing Published functional studies demonstrate an adverse effect on hydrogen bonds and Liprin-alpha2 binding thus affecting cell survival (Guo et al., 2023); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33090494, 19377476, 23406872, 24505460, 37190086)
OMIM RCV000012289 SCV000032523 pathogenic FG syndrome 4 2009-05-01 no assertion criteria provided literature only

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