Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000816206 | SCV000956703 | benign | Gorlin syndrome | 2023-03-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001012191 | SCV001172614 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-13 | criteria provided, single submitter | clinical testing | The p.A521T variant (also known as c.1561G>A), located in coding exon 11 of the PTCH1 gene, results from a G to A substitution at nucleotide position 1561. The alanine at codon 521 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Victorian Clinical Genetics Services, |
RCV000816206 | SCV002769342 | uncertain significance | Gorlin syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as VUS – 3B. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0107 - This gene is known to be associated with autosomal dominant disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from an alanine to a threonine (exon 11). (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (1 heterozygote, 0 homozygotes). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (1 heterozygote, 0 homozygotes). (N) 0502 - Missense variant with conflicting in silico predictions and/or uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif (patched domain; PDB). (N) 0708 – A comparable variant (p.Ala455Val) has been previously reported as a variant of uncertain significance (ClinVar). (N) 0804 - Variant has previously been described as a variant of uncertain significance (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is maternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign |