ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.2695A>G (p.Ile899Val)

gnomAD frequency: 0.00001  dbSNP: rs765371196
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000791706 SCV000930966 likely benign Gorlin syndrome 2024-09-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433914 SCV002745347 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-20 criteria provided, single submitter clinical testing The p.I899V variant (also known as c.2695A>G), located in coding exon 16 of the PTCH1 gene, results from an A to G substitution at nucleotide position 2695. The isoleucine at codon 899 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477709 SCV004219193 uncertain significance not provided 2023-05-23 criteria provided, single submitter clinical testing In the published literature, this variant has been reported in at least one individual with Peters’ anomaly (PMIDs: 26893459 (2016) and 35170016 (2022)). In vivo functional studies indicated that this variant results in partial loss of PTCH1 function (PMID: 26893459 (2016)). The frequency of this variant in the general population, 0.000016 (4/251388 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is deleterious or benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Paul Sabatier University EA-4555, Paul Sabatier University RCV000207421 SCV000259170 likely pathogenic Irido-corneo-trabecular dysgenesis 2013-01-01 flagged submission clinical testing rare variant, functional studies demonstrating is deleterious effect on protein.

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