ClinVar Miner

Submissions for variant NM_000264.5(PTCH1):c.1913G>A (p.Arg638His) (rs145766839)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001087187 SCV000260535 likely benign Gorlin syndrome 2020-11-16 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000592243 SCV000708880 likely benign not specified 2017-11-03 criteria provided, single submitter clinical testing
GeneDx RCV000592243 SCV000730309 likely benign not specified 2017-11-10 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756577 SCV000884424 uncertain significance not provided 2018-01-24 criteria provided, single submitter clinical testing The c.1913G>A; p.Arg638His variant (rs145766839), to our knowledge, is not reported in the medical literature, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 0.1% (identified on 27 out of 24,020 chromosomes) and is classified as likely benign in ClinVar (ID 220182). The arginine at position 638 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Arg638His variant on protein structure and function provide conflicting information (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Arg638His variant cannot be determined with certainty.
Ambry Genetics RCV001013676 SCV001174293 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-23 criteria provided, single submitter clinical testing The p.R638H variant (also known as c.1913G>A), located in coding exon 14 of the PTCH1 gene, results from a G to A substitution at nucleotide position 1913. The arginine at codon 638 is replaced by histidine, 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.

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