Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV004017429 | SCV000204220 | uncertain significance | not provided | 2022-09-07 | criteria provided, single submitter | clinical testing | The p.Lys991Asn variant in MYH7 has been identified in 1 neonate with dilated cardiomyopathy (DCM; Pugh 2014 PMID: 24503870, Walsh 2017 PMID: 27532257, LMM data). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 177895) and has been identified in 0.001% (1/68022) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org, v.3.1.2). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PM2_Supporting. |
| Color Diagnostics, |
RCV001184476 | SCV001350449 | uncertain significance | Cardiomyopathy | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 991 of the MYH7 protein. Computational prediction tools indicate that this variant may have an uncertain impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with dilated cardiomyopathy (PMID: 24503780, 27532257). This variant has not been identified 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. |
| Labcorp Genetics |
RCV001345824 | SCV001539970 | uncertain significance | Hypertrophic cardiomyopathy | 2022-04-16 | 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 lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 991 of the MYH7 protein (p.Lys991Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 24503780). ClinVar contains an entry for this variant (Variation ID: 177895). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
| Fulgent Genetics, |
RCV002498742 | SCV002806842 | 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 | 2021-12-23 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001184476 | SCV004836244 | uncertain significance | Cardiomyopathy | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with asparagine at codon 991 of the MYH7 protein. Computational prediction tools indicate that this variant may have an uncertain impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual affected with dilated cardiomyopathy (PMID: 24503780, 27532257). This variant has not been identified 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. |