Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158644 | SCV000208579 | uncertain significance | not provided | 2018-01-12 | criteria provided, single submitter | clinical testing | p.Val1407Ile (GTT>ATT): c.4219 G>A in exon 31 of the MYH7 gene (NM_000257.2). A variant of unknown significance has been identified in the MYH7 gene. The V1407I variant has not been published as a mutation or as a benign polymorphism to our knowledge. The V1407I variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In addition, this substitution occurs at a position that is completely conserved in mammals. Moreover, a missense mutation in a nearby residue L1414M has been reported in association with HCM, supporting the functional importance of this region of the protein. Nevertheless, the V1407I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s). |
Invitae | RCV000822740 | SCV000963556 | uncertain significance | Hypertrophic cardiomyopathy | 2023-11-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1407 of the MYH7 protein (p.Val1407Ile). This variant is present in population databases (rs730880795, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 181249). 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 expected to disrupt MYH7 protein function with a positive 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. |
Color Diagnostics, |
RCV001180569 | SCV001345527 | uncertain significance | Cardiomyopathy | 2023-11-15 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 1407 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function. 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: 33495597). This variant has been identified in 5/282872 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. |
Fulgent Genetics, |
RCV002484976 | SCV002793207 | uncertain significance | Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy | 2021-10-13 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV001180569 | SCV004823361 | uncertain significance | Cardiomyopathy | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 1407 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: 33495597). This variant has been identified in 5/282872 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. |