ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3148C>T (p.Arg1050Ter)

gnomAD frequency: 0.00001  dbSNP: rs730880767
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158589 SCV000208524 uncertain significance not provided 2017-01-06 criteria provided, single submitter clinical testing p.Arg1050Stop (CGA>TGA): c.3148 C>T in exon 25 of the MYH7 gene (NM_000257.2). A variant of unknown significance has been identified in the MYH7 gene. The R1050X variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. R1050X 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). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Color Diagnostics, LLC DBA Color Health RCV001181611 SCV001346792 uncertain significance Cardiomyopathy 2022-10-10 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 25 of the MYH7 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 4/251484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Clinical significance of loss-of-function MYH7 truncation variants in autosomal dominant cardiovascular disorders is not clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV002515072 SCV003498886 uncertain significance Hypertrophic cardiomyopathy 2023-06-05 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. ClinVar contains an entry for this variant (Variation ID: 181214). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs730880767, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Arg1050*) 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.

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