ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.4252G>A (p.Val1418Ile)

gnomAD frequency: 0.00014  dbSNP: rs369882883
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084929 SCV000260005 benign Gorlin syndrome 2024-02-01 criteria provided, single submitter clinical testing
GeneDx RCV000484134 SCV000565437 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing This variant is denoted PTCH1 c.4252G>A at the cDNA level, p.Val1418Ile (V1418I) at the protein level, and results in the change of a Valine to an Isoleucine (GTC>ATC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PTCH1 Val1418Ile was not observed at significant allele frequency in the NHLBI Exome Sequencing Project or in 1000 Genomes. Since Valine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. PTCH1 Val1418Ile occurs at a position that is conserved in mammals and is not located in a known functional domain (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether PTCH1 Val1418Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561736 SCV000664954 likely benign Hereditary cancer-predisposing syndrome 2019-03-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Sema4, Sema4 RCV000561736 SCV002535164 likely benign Hereditary cancer-predisposing syndrome 2021-12-16 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV004547474 SCV004726193 likely benign PTCH1-related disorder 2019-07-08 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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