Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000545041 | SCV000648264 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1466 of the MYH6 protein (p.Gln1466Glu). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 470540). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Ambry Genetics | RCV002330926 | SCV002633072 | uncertain significance | Cardiovascular phenotype | 2021-05-05 | criteria provided, single submitter | clinical testing | The c.4395_4396delGCinsAG variant (also known as p.Q1466E), located in coding exon 29 of the MYH6 gene, results from an in-frame deletion of GC and insertion of AG at nucleotide positions 4395 to 4396. This results in the substitution of the glutamine residue for a glutamic acid residue at codon 1466, an amino acid with highly similar properties. Based on data from gnomAD, this allele has an overall frequency of 0.0008% (2/250274) total alleles studied. The highest observed frequency was 0.00006% (1/16190) of African/African American alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002497163 | SCV002794521 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-09-22 | criteria provided, single submitter | clinical testing |