Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672768 | SCV000797906 | uncertain significance | Autosomal recessive congenital ichthyosis 1 | 2018-02-14 | criteria provided, single submitter | clinical testing | |
| Institute for Human Genetics and Genomic Medicine, |
RCV000672768 | SCV002549099 | likely pathogenic | Autosomal recessive congenital ichthyosis 1 | 2022-06-23 | criteria provided, single submitter | clinical testing | The detected change is reported in the dbSNP database (dbSNP151 as of 06/23/2022) with the designation rs778635368. In gnomAD it is listed with a frequency of 0.001061% (3/282772) (as of 06/23/2022). This variant has already been described several times in the literature in patients with ichthyosis (Hennies et al., 1998, Yamamoto et al., 2012). It is located in a mutation hotspot and is bioinformatically classified as "probably disease-causing" (PolyPhen2, Mutation Taster, SIFT, CADDphred 29.3). Based on the current state of knowledge, the variant can be classified as a "likely pathogenic variant" (ACMG criteria). |
| Baylor Genetics | RCV000672768 | SCV004203774 | pathogenic | Autosomal recessive congenital ichthyosis 1 | 2024-02-19 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003558520 | SCV004296328 | pathogenic | not provided | 2023-08-16 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with lamellar ichthyosis (PMID: 9545389, 11064247, 21895619). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs778635368, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 144 of the TGM1 protein (p.Gly144Arg). ClinVar contains an entry for this variant (Variation ID: 556724). For these reasons, this variant has been classified as Pathogenic. 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. |