Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000158866 | SCV000208801 | likely pathogenic | not provided | 2011-07-12 | criteria provided, single submitter | clinical testing | This mutation is denoted p.Glu1490Asp (E1490D) at the protein level and c.4470 G>C at the cDNA level. The Glu1490Asp variant in the MYH7 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Although Glu1490Asp results in a conservative amino acid substitution of one negatively charged, polar amino acid with another, it occurs at a position that is highly conserved throughout evolution. Additionally, in silico analysis predicts Glu1490Asp to be probably damaging to the protein structure/function. Mutations in nearby codons (Tyr1488Cys, Ser1491Cys, Glu1496Ala) have been reported in association with left ventricular non-compaction and HCM, further supporting the functional importance of this region of the protein. Glu1490Asp was not observed in up to 400 alleles from control individuals of African American and Caucasian ancestry tested at GeneDx, indicating it is not a common benign polymorphism in these populations. In summary, while the Glu1490Asp variant is a good candidate for a disease-causing mutation, we cannot unequivocally determine whether Glu1490Asp is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s). |
Laboratory for Molecular Medicine, |
RCV000219927 | SCV000272050 | uncertain significance | not specified | 2015-02-02 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu1490As p variant in MYH7 has not been previously reported in individuals with cardiomyo pathy and was absent from large population studies. Glutamic acid (Glu) at posit ion 1490 is highly conserved in mammals and across evolutionarily distant specie s and the change to aspartic acid (Asp) was predicted to be pathogenic using a c omputational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). In summary , while there is some suspicion for a pathogenic role, the clinical significance of the p.Glu1490Asp variant is uncertain. |