Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000541411 | SCV000648278 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2024-06-29 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1859 of the MYH6 protein (p.Asp1859Asn). 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 variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 470550). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MYH6 protein function. 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. |
Ai |
RCV002223871 | SCV002502128 | uncertain significance | not provided | 2022-02-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002350323 | SCV002650034 | uncertain significance | Cardiovascular phenotype | 2023-10-20 | criteria provided, single submitter | clinical testing | The p.D1859N variant (also known as c.5575G>A), located in coding exon 35 of the MYH6 gene, results from a G to A substitution at nucleotide position 5575. The aspartic acid at codon 1859 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |