Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678313 | SCV000804372 | uncertain significance | Gorlin syndrome; Holoprosencephaly 7 | 2018-03-01 | criteria provided, single submitter | provider interpretation | This variant was identified in a 9 year old male with autism spectrum disorder and hyperkinesis. The variant is absent from the gnomAD database, and it was found to be de novo (with maternity and paternity confirmed). Computational prediction models are inconsistent. This variant has not been reported previously to our knowledge and specific features of Gorlin syndrome have not been observed in this patient. |
| Invitae | RCV001246822 | SCV001420209 | uncertain significance | Gorlin syndrome | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 281 of the PTCH1 protein (p.Met281Thr). This variant is not present in population databases (gnomAD no frequency). 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: 560251). 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. |
| Ambry Genetics | RCV002442403 | SCV002677802 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-05 | criteria provided, single submitter | clinical testing | The p.M281T variant (also known as c.842T>C), located in coding exon 6 of the PTCH1 gene, results from a T to C substitution at nucleotide position 842. The methionine at codon 281 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |