Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497521 | SCV000590648 | uncertain significance | not provided | 2017-06-21 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the MYOT gene. The I253T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I253T variant is observed in 1/66736 (0.002%) alleles from individuals of European background, in teh ExAC dataset (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I253T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001217128 | SCV001388959 | uncertain significance | Myofibrillar myopathy 3 | 2022-11-08 | criteria provided, single submitter | clinical testing | 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. 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 MYOT protein function. ClinVar contains an entry for this variant (Variation ID: 432877). This variant has not been reported in the literature in individuals affected with MYOT-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 253 of the MYOT protein (p.Ile253Thr). |