ClinVar Miner

Submissions for variant NM_003738.5(PTCH2):c.523C>T (p.Arg175Trp)

gnomAD frequency: 0.00001  dbSNP: rs777212373
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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 RCV001299728 SCV001488833 uncertain significance Gorlin syndrome 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 175 of the PTCH2 protein (p.Arg175Trp). This variant is present in population databases (rs777212373, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with PTCH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1003202). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001299728 SCV002012440 uncertain significance Gorlin syndrome 2021-10-28 criteria provided, single submitter clinical testing The PTCH2 c.523C>T (p.Arg175Trp) missense change has a maximum subpopulation frequency of 0.0085% in gnomAD v2.1.1 https://gnomad.broadinstitute.org/variant/1-45297649-G-A). Six of seven in silico tools predict a deleterious effect of this variant on protein function (PP3), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with Gorlin syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PP3.
Fulgent Genetics, Fulgent Genetics RCV005029877 SCV005651288 uncertain significance Basal cell carcinoma, susceptibility to, 1; Medulloblastoma 2024-06-06 criteria provided, single submitter clinical testing

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