ClinVar Miner

Submissions for variant NM_001083602.2(PTCH1):c.4-1707G>T (rs587780708)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484179 SCV000573529 uncertain significance not provided 2017-02-20 criteria provided, single submitter clinical testing This variant is denoted PTCH1 c.56G>T at the cDNA level, p.Gly19Val (G19V) at the protein level, and results in the change of a Glycine to a Valine (GGC>GTC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. PTCH1 Gly19Val occurs at a position that has low coverage in the NHLBI Exome Sequencing Project, therefore we cannot assess frequency in the general population. Since Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. PTCH1 Gly19Val occurs at a position that is not conserved and is located in cytoplasmic topological domain and in a glycine-rich region of compositional bias (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 Gly19Val is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000123041 SCV000166336 uncertain significance Gorlin syndrome 2018-04-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 19 of the PTCH1 protein (p.Gly19Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with PTCH1-related disease. ClinVar contains an entry for this variant (Variation ID: 135905). 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: "Tolerated"; PolyPhen-2: "Probably 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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