Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV001171202 | SCV001333899 | uncertain significance | Cardiomyopathy | 2018-02-22 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001171202 | SCV001353816 | uncertain significance | Cardiomyopathy | 2023-03-30 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 1351 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 16858239, 18533079). This variant has been identified in 12/251344 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Invitae | RCV001338291 | SCV001531951 | uncertain significance | Hypertrophic cardiomyopathy | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1351 of the MYH7 protein (p.Thr1351Met). This variant is present in population databases (rs370403289, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 16858239). ClinVar contains an entry for this variant (Variation ID: 161324). 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 MYH7 protein function with a negative predictive value of 95%. 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. |
CSER _CC_NCGL, |
RCV000148705 | SCV000190434 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2014-06-01 | no assertion criteria provided | research |