ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.4049G>A (p.Arg1350Gln)

gnomAD frequency: 0.00001  dbSNP: rs978722722
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000699814 SCV000828542 uncertain significance Gorlin syndrome 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1350 of the PTCH1 protein (p.Arg1350Gln). This variant is not present in population databases (gnomAD no frequency). 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: 577136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTCH1 protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV000764836 SCV000895992 uncertain significance Basal cell carcinoma, susceptibility to, 1; Gorlin syndrome; Holoprosencephaly 7 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001021745 SCV001183397 likely benign Hereditary cancer-predisposing syndrome 2023-01-19 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.
PreventionGenetics, part of Exact Sciences RCV004547867 SCV004779060 likely benign PTCH1-related disorder 2023-02-21 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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