Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413671 | SCV000491833 | uncertain significance | not provided | 2017-05-31 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the MYH7 gene. The K598E variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The K598E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K598E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this variant has not been identified in a significant number of affected individuals, and there are no functional studies or segregation data available to clarify the role of this variant in disease. |
New York Genome Center | RCV001836812 | SCV002097655 | uncertain significance | Dilated cardiomyopathy 1S | 2020-07-09 | criteria provided, single submitter | clinical testing | The heterozygous p.Lys598Glu missense variant identified in the MYH7 gene has not been reported in affected individuals in the literature to the best of our knowledge. The variant is reported in ClinVar as a variant of uncertain significance (Variation ID:373253). The variant is absent from gnomAD(v3) database indicating it is an extremely rare allele in populations represented in the database. The p.Lys598Glu variant affects an evolutionarily conserved reside and is predicted deleterious by multiple in silico prediction tools. Based on the available evidence, the p.Lys598Glu variant in MYH7 is assessed as a variant of uncertain significance. |