Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000151253 | SCV000199159 | uncertain significance | not specified | 2018-11-29 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu967Lys variant in MYH7 has been identified by our laboratory in 1 individual with clin ical features of adult onset HCM and 1 individual with neonatal onset HCM (Alfar es 2015, Walsh 2017) and was absent from large population studies. Glutamic acid (Glu) at position 967 is highly conserved in mammals and across evolutionarily distant species and the change to lysine (Lys) was predicted to be pathogenic us ing a computational tool clinically validated by our laboratory. This tool's pat hogenic 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 signi ficance of the p.Glu967Lys variant is uncertain. ACMG/AMP Criteria applied: PS4_ Supporting, PM2, PP3. |
Invitae | RCV002514912 | SCV003269076 | uncertain significance | Hypertrophic cardiomyopathy | 2023-08-14 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 164309). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 25611685). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 967 of the MYH7 protein (p.Glu967Lys). |