ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.1660A>T (p.Ser554Cys)

dbSNP: rs1060502282
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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 RCV000464727 SCV000549070 uncertain significance Gorlin syndrome 2024-07-21 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 554 of the PTCH1 protein (p.Ser554Cys). 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: 409172). 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.
Ambry Genetics RCV001012559 SCV001173026 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-14 criteria provided, single submitter clinical testing The p.S554C variant (also known as c.1660A>T), located in coding exon 12 of the PTCH1 gene, results from an A to T substitution at nucleotide position 1660. The serine at codon 554 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005044682 SCV005679696 uncertain significance Basal cell carcinoma, susceptibility to, 1; Holoprosencephaly 7; Basal cell nevus syndrome 1 2024-04-25 criteria provided, single submitter clinical testing

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