Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000154423 | SCV000204091 | uncertain significance | not specified | 2016-09-01 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Ile521Thr variant in MYH7 has been identified by our laboratory in 1 Caucasian individual with HCM and 1 Caucasian individual with features of ARVC. It was absent from l arge population studies. Isoleucine (Ile) at position 521 is highly conserved in mammals and across evolutionarily distant species and the change to threonine ( Thr) was predicted to be pathogenic using a computational tool clinically valida ted by our laboratory. This tool's pathogenic prediction is estimated to be corr ect 94% of the time (Jordan 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Ile521Thr variant is unce rtain. |
| Invitae | RCV000690654 | SCV000818352 | uncertain significance | Hypertrophic cardiomyopathy | 2022-11-09 | 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: 177795). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy and in an individual referred for genetic testing for this condition (PMID: 25611685, 27532257). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 521 of the MYH7 protein (p.Ile521Thr). |