Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664924 | SCV000788958 | uncertain significance | Autosomal recessive congenital ichthyosis 1 | 2016-12-23 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000664924 | SCV004203732 | likely pathogenic | Autosomal recessive congenital ichthyosis 1 | 2024-02-12 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003558483 | SCV004296314 | pathogenic | not provided | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 544 of the TGM1 protein (p.Tyr544Cys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of congenital ichthyosis (PMID: 18948357, 30302839; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550231). 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 expected to disrupt TGM1 protein function with a positive predictive value of 95%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |