Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000415011 | SCV000493042 | likely pathogenic | Brachydactyly; Alopecia areata; Pear-shaped nose; Proportionate short stature | 2014-02-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000695017 | SCV000823491 | pathogenic | Trichorhinophalangeal syndrome, type III; Trichorhinophalangeal dysplasia type I | 2023-07-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Tricho-Rhino-Phalangeal Syndrome (PMID: 11112658, 30541476). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as c.2755G>A (p.Ala919Thr). ClinVar contains an entry for this variant (Variation ID: 374202). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TRPS1 protein function. This variant disrupts the p.Ala932 amino acid residue in TRPS1. Other variant(s) that disrupt this residue have been observed in individuals with TRPS1-related conditions (PMID: 18946009, 24502542, 28468609), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 932 of the TRPS1 protein (p.Ala932Thr). |
Gene |
RCV000505377 | SCV000599581 | not provided | Trichorhinophalangeal dysplasia type I | no assertion provided | literature only |