ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.2558A>G (p.Gln853Arg)

gnomAD frequency: 0.00001  dbSNP: rs587778628
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462194 SCV000549087 uncertain significance Gorlin syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 853 of the PTCH1 protein (p.Gln853Arg). This variant is present in population databases (rs587778628, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 135096). 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 tolerated. 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.
Sema4, Sema4 RCV002255299 SCV002526855 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-23 criteria provided, single submitter curation
Ambry Genetics RCV002255299 SCV002741140 likely benign Hereditary cancer-predisposing syndrome 2023-01-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx RCV003126502 SCV003803312 uncertain significance not provided 2023-05-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 24728327, 8906794)
ITMI RCV000121887 SCV000086090 not provided not specified 2013-09-19 no assertion provided reference population

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