ClinVar Miner

Submissions for variant NM_003738.5(PTCH2):c.446T>A (p.Leu149His)

gnomAD frequency: 0.00004  dbSNP: rs111283762
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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 RCV000546322 SCV000623089 uncertain significance Gorlin syndrome 2023-01-01 criteria provided, single submitter clinical testing 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 PTCH2 protein function. ClinVar contains an entry for this variant (Variation ID: 453941). This variant has not been reported in the literature in individuals affected with PTCH2-related conditions. This variant is present in population databases (rs111283762, gnomAD 0.008%). This sequence change replaces leucine, which is neutral and non-polar, with histidine, which is basic and polar, at codon 149 of the PTCH2 protein (p.Leu149His). 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 RCV000546322 SCV004171425 uncertain significance Gorlin syndrome 2023-11-21 criteria provided, single submitter clinical testing The PTCH2 c.446T>A (p.Leu149His) missense change has a maximum subpopulation frequency of 0.0080% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with nevoid basal cell carcinoma syndrome.??In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.??
Fulgent Genetics, Fulgent Genetics RCV005027621 SCV005653356 uncertain significance Basal cell carcinoma, susceptibility to, 1; Medulloblastoma 2024-05-02 criteria provided, single submitter clinical testing

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