ClinVar Miner

Submissions for variant NM_001083602.2(PTCH1):c.126A>G (p.Ile42Met) (rs144182921)

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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 RCV000574912 SCV000664951 likely benign Hereditary cancer-predisposing syndrome 2016-12-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585211 SCV000693293 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
Invitae RCV000167969 SCV000218617 uncertain significance Gorlin syndrome 2018-11-12 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 108 of the PTCH1 protein (p.Ile108Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs144182921, ExAC 0.02%), 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: 188114). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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