Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000473507 | SCV000546154 | uncertain significance | Hypertrophic cardiomyopathy 14 | 2023-05-19 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs372794975, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 1200 of the MYH6 protein (p.Asp1200His). 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 MYH6 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 407151). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). |
Laboratory for Molecular Medicine, |
RCV000607798 | SCV000711402 | uncertain significance | not specified | 2017-05-18 | criteria provided, single submitter | clinical testing | The p.Asp1200His variant in MYH6 has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.1% (14/23478) of African chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org/; dbSNP rs372794975). This variant has been reported in ClinVar (Variation ID: 407151) as of uncertain significance. Computational prediction tools and co nservation analysis suggest that the p.Asp1200His variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, the clinical significance of the p.Asp1200His variant is uncertain. |
Gene |
RCV001595007 | SCV001829319 | uncertain significance | not provided | 2023-05-02 | criteria provided, single submitter | clinical testing | Reported in a pediatric patient with dilated cardiomyopathy; additional clinical data were not described (Burstein et al., 2021); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32746448) |
Ambry Genetics | RCV002451098 | SCV002614914 | uncertain significance | Cardiovascular phenotype | 2023-08-01 | criteria provided, single submitter | clinical testing | The p.D1200H variant (also known as c.3598G>C), located in coding exon 24 of the MYH6 gene, results from a G to C substitution at nucleotide position 3598. The aspartic acid at codon 1200 is replaced by histidine, an amino acid with similar properties. This variant has been detected in a pediatric dilated cardiomyopathy case and in a pediatric restrictive cardiomyopathy case; however, detail was limited (Burstein DS et al. Pediatr Res. 2021 May;89(6):1470-1476; Ware SM et al. Am J Hum Genet. 2022 Feb;109(2):282-298). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002489034 | SCV002778356 | uncertain significance | Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to | 2021-07-29 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001595007 | SCV004236698 | uncertain significance | not provided | 2023-07-12 | criteria provided, single submitter | clinical testing | |
Clinical Genetics, |
RCV001595007 | SCV001918357 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001595007 | SCV001969541 | uncertain significance | not provided | no assertion criteria provided | clinical testing |