ClinVar Miner

Submissions for variant NM_000257.3(MYH7):c.1322C>T (p.Thr441Met) (rs121913653)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000777877 SCV000913885 likely benign Cardiomyopathy 2018-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000767122 SCV000617059 uncertain significance not provided 2016-02-12 criteria provided, single submitter clinical testing The T441M variant in the MYH7 gene has been reported previously in one child with skeletal myopathy with mild atrial enlargement and septal thickness in the 95th percentile and was absent in 200 control chromosomes (Darin et al., 2007). Expression studies showed that mutated and wild-type alleles were equally expressed at the mRNA level (Darin et al., 2007). The T441M variant has also been reported in one Chinese family with hypertrophic cardiomyopathy (Fan et al., 2011; Feng et al., 2011). The T441M variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The T441M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position in the myosin motor domain that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in nearby residues (N437D, M439T, M439R, V440M, R442C, R442H, I443T, N444S) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret T441M as a variant of uncertain significance, which may be related to the muscle weakness and atrophy reported in this individual.
GeneReviews RCV000192200 SCV000223105 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only
Invitae RCV000168124 SCV000218781 likely benign Hypertrophic cardiomyopathy 2018-01-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035714 SCV000059365 likely benign not specified 2017-08-30 criteria provided, single submitter clinical testing MYH7 1322C>T: Disclaimer: This variant has not undergone a full assessment. The following are preliminary notes: Classified as VUS3 in 2014 and no new pubs since then. Has a max MAF in ExAC of 0.15% (13 alleles) and gnomad of 0.27% (53 alleles) - frequency too high for disease.
OMIM RCV000192200 SCV000035437 pathogenic Myopathy, distal, 1 2007-06-05 no assertion criteria provided literature only

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