Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001047006 | SCV001210935 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2022-11-03 | 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. This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 801 of the MYH6 protein (p.Ile801Phe). This variant is present in population databases (rs75487328, gnomAD 0.006%). 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: 844213). 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 MYH6 protein function. |
| Ambry Genetics | RCV002429619 | SCV002731907 | uncertain significance | Cardiovascular phenotype | 2024-04-27 | criteria provided, single submitter | clinical testing | The p.I801F variant (also known as c.2401A>T), located in coding exon 18 of the MYH6 gene, results from an A to T substitution at nucleotide position 2401. The isoleucine at codon 801 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001357321 | SCV001552762 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The MYH6 p.Ile801Phe variant was not identified in the literature nor was it identified in the ClinVar, COGR, Cosmic, MutDB or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs75487328) and in control databases in 2 of 251450 chromosomes at a frequency of 0.000008 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: Latino in 2 of 34590 chromosomes (freq: 0.000058), but was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Other, and South Asian populations. The p.Ile801 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, and MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |