Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001230042 | SCV001402509 | uncertain significance | Hypertrophic cardiomyopathy | 2022-03-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 619 of the MYH7 protein (p.Thr619Ile). 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 variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 155813). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). This variant is present in population databases (rs541143322, gnomAD 0.004%). |
Color Diagnostics, |
RCV001525514 | SCV001735651 | uncertain significance | Cardiomyopathy | 2023-12-06 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 619 of the MYH7 protein. Computational prediction tool indicates that this variant may have a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in three individuals affected with hypertrophic cardiomyopathy (PMID: 27532257). This variant has been identified in 5/251434 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. |
Petrovsky National Research Centre of Surgery, |
RCV003448904 | SCV004176288 | uncertain significance | Primary dilated cardiomyopathy | 2023-06-06 | criteria provided, single submitter | clinical testing | Heterozygous variant NM_000257:c.1856C>T (p.Thr619Ile) in the MYH7 gene was found on WES data in male proband (39 y.o., Caucasian) with Dilated Cardiomyopathy. Additional rare candidate variant NM_000256:c.93C>A (p.Ala31=) (Class III of pathogenicity) in the MYBPC3 gene was found in this proband. NM_000257:c.1856C>T variant is in The Genome Aggregation Database (gnomAD) v2.1.1 with total MAF 0.00001989 (Date of access 06-06-2023). Clinvar contains entry on this variant (Variation ID: 155813). This variant has been reported in 1 study in 3 individuals with consistent phenotype (PMID: 27532257). Most in silico predictors show benign result of the protein change (varsome.com). In accordance with Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen’s Inherited Cardiomyopathy Expert Panel (PMID: 29300372) this variant is classified as Variant of Uncertain Significance (VUS) with following criteria selected: PM1, PM2, PS4_Supporting, BP4. |
Blueprint Genetics | RCV000143921 | SCV000188796 | likely benign | Primary familial hypertrophic cardiomyopathy | 2013-12-20 | no assertion criteria provided | clinical testing |