Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156190 | SCV000205906 | uncertain significance | not specified | 2013-12-27 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Pathogenic. The Gln1704X va riant in MYH7 has not been reported in individuals with cardiomyopathy or in lar ge European American and African American populations (NHLBI exome sequencing pr oject). This nonsense variant leads to a premature termination codon at position 1704, which is predicted to lead to a truncated or absent protein. It should be noted that loss of function variants in the MYH7 gene are very rare and therefo re, their phenotypic spectrum is unknown. In the few reported cases with MYH7 no nsense variants, all were present in trans along with another MYH7 variant in a severely affected, young individual and in all cases the nonsense variant was in herited from an unaffected parent, suggesting that heterozygous loss of function of MYH7 may not be disease causing (Houghs 2005, Nishi 1995, LMM unpublished da ta). In summary, although this variant severely impacts the protein, additional studies are needed to fully assess its clinical significance. |
| Gene |
RCV000766466 | SCV000208617 | uncertain significance | not provided | 2017-01-08 | criteria provided, single submitter | clinical testing | p.Gln1704Stop (CAG>TAG): c.5110 C>T in exon 35 of the MYH7 gene (NM_000257.2). The Gln1704Stop variant in the MYH7 gene has not been reported as a disease-causing mutation or as benign polymorphism to our knowledge. Gln1704Stop is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Although nonsense mutations in the MYH7 gene have been reported in association with cardiomyopathy, the vast majority of mutations in MYH7 are missense changes. Furthermore, various studies have conflicting hypotheses regarding MYH7 haploinsufficiency leading to cardiomyopathy (Nishi H et al., 1995; Waldmuller S et al., 2011). With the clinical and molecular information available at this time, we cannot definitively determine if Gln1704Stop is a disease-causing mutation or a rare benign variant. The variant is found in DCM panel(s). |