Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000215486 | SCV000272044 | uncertain significance | not specified | 2014-12-17 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Asp1198fs variant in MYH7 has not been previously reported in individuals with cardiomyop athy. This variant deletes 2 bases and inserts 7, resulting in a frameshift, whi ch is predicted to alter the protein?s amino acid sequence beginning at position 1198 and to lead to a premature termination codon 18 amino acids downstream. Th is alteration is then predicted to lead to a truncated or absent protein. It sho uld be noted that loss of function variants in the MYH7 gene are very rare and t herefore, their phenotypic spectrum is incompletely characterized. Emerging evid ence suggests that truncating variants in MYH7 have little/no effect on their ow n but result in severe and early onset disease when a second variant is present on the other copy of the gene (LMM unpublished data). In summary, while this var iant severely impacts the protein, its clinical significance is uncertain. |
Invitae | RCV000811114 | SCV000951362 | uncertain significance | Hypertrophic cardiomyopathy | 2022-02-24 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs755646089, gnomAD 0.002%). 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: 228908). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This sequence change creates a premature translational stop signal (p.Asp1198Argfs*18) in the MYH7 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. |