ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3621C>G (p.Ile1207Met) (rs529700838)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480443 SCV000565290 likely pathogenic not provided 2015-09-14 criteria provided, single submitter clinical testing The I1207M likely pathogenic variant in the MYH7 gene has been previously reported in an individual with HCM progressing to heart failure and requiring a heart transplant, and was not detected in 800 control alleles (Melacini et al., 2010). The I1209M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant occurs at a position that is conserved across species and in silico predictions this variant is probably damaging to the protein structure/function. Furthermore, missense variants in nearby residues (E1205K, D1208N, N1209S, Q1215H) 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. However, the I1207M is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties.Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Ambry Genetics RCV000620521 SCV000736661 uncertain significance Cardiovascular phenotype 2016-08-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Mendelics RCV000989188 SCV001139411 likely pathogenic Familial hypertrophic cardiomyopathy 1 2019-05-28 criteria provided, single submitter clinical testing

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