Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
St. |
RCV000761023 | SCV000890938 | uncertain significance | Retinoblastoma | 2016-03-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001022254 | SCV001183969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-16 | criteria provided, single submitter | clinical testing | The p.V1435M variant (also known as c.4303G>A), located in coding exon 23 of the PTCH1 gene, results from a G to A substitution at nucleotide position 4303. The valine at codon 1435 is replaced by methionine, an amino acid with highly similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). This amino acid position is 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. |
Invitae | RCV001036592 | SCV001199965 | uncertain significance | Gorlin syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1435 of the PTCH1 protein (p.Val1435Met). This variant is present in population databases (rs587778632, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PTCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 135107). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTCH1 protein function with a negative predictive value of 95%. 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. |
ITMI | RCV000121902 | SCV000086106 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |