ClinVar Miner

Submissions for variant NM_001083602.2(PTCH1):c.3721C>T (p.Pro1241Ser) (rs574880967)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567632 SCV000674515 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-07 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000764839 SCV000895995 uncertain significance Basal cell carcinoma, multiple; Gorlin syndrome; Holoprosencephaly 7 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000119211 SCV000153953 uncertain significance Gorlin syndrome 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1307 of the PTCH1 protein (p.Pro1307Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs574880967, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with PTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 132753). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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