Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001968746 | SCV002255147 | uncertain significance | not provided | 2022-09-27 | 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 expected to disrupt MYH14 protein function. ClinVar contains an entry for this variant (Variation ID: 1467924). This variant has not been reported in the literature in individuals affected with MYH14-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 arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1158 of the MYH14 protein (p.Arg1158Cys). |
| Gene |
RCV001968746 | SCV002578390 | uncertain significance | not provided | 2022-04-05 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV002571224 | SCV003750778 | uncertain significance | Inborn genetic diseases | 2020-08-04 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change:_x000D_ _x000D_ The c.3472C>T (p.R1158C) alteration is located in exon 26 (coding exon 25) of the MYH14 gene. This alteration results from a C to T substitution at nucleotide position 3472, causing the arginine (R) at amino acid position 1158 to be replaced by a cysteine (C). The alteration has been observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD) database, the MYH14 c.3472C>T alteration was observed in 0.0032% (8/248,486) of total alleles studied. The altered amino acid is not conserved throughout evolution:_x000D_ _x000D_ The p.R1158 amino acid is not conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.R1158C alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |