Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002359580 | SCV002619771 | uncertain significance | Cardiovascular phenotype | 2023-01-25 | criteria provided, single submitter | clinical testing | The p.R1346Q variant (also known as c.4037G>A), located in coding exon 27 of the MYH6 gene, results from a G to A substitution at nucleotide position 4037. The arginine at codon 1346 is replaced by glutamine, an amino acid with highly similar properties. This variant has been detected in a patient from a pediatric dilated cardiomyopathy cohort who also had variants in other cardiac-related genes (Herkert JC et al. Genet. Med., 2018 11;20:1374-1386). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003775802 | SCV004648750 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1346 of the MYH6 protein (p.Arg1346Gln). This variant is present in population databases (no rsID available, gnomAD 0.005%). This missense change has been observed in individual(s) with clinical features of MYH6-related conditions (PMID: 36178741). ClinVar contains an entry for this variant (Variation ID: 1737251). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |