ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3994G>A (p.Ala1332Thr) (rs397516198)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035880 SCV000059531 uncertain significance not specified 2015-10-05 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000766755 SCV000279571 uncertain significance not provided 2016-02-17 criteria provided, single submitter clinical testing The A1332T variant has been reported in one patient with dilated cardiomyopathy (DCM) (Waldmuller et al., 2011). However, no other clinical or segregation information was provided. In addition, the A1332T variant has been classified as a variant of uncertain significance by another clinical laboratory in ClinVar (Landrum et al., 2014). The A1332T 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. The A1332T 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. This substitution occurs at a position that is conserved across species. Finally, in silico analysis predicts this variant is probably damaging to the protein structure/function.
Invitae RCV000685068 SCV000812540 uncertain significance Hypertrophic cardiomyopathy 2019-11-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1332 of the MYH7 protein (p.Ala1332Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs397516198, ExAC 0.003%). This variant has been observed in individuals affected with MYH7-related conditions (PMID: 21750094, 27532257). ClinVar contains an entry for this variant (Variation ID: 42986). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not available"; Align-GVGD: "Class C0"). 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.
Color RCV001178113 SCV001342469 uncertain significance Cardiomyopathy 2019-08-22 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000766755 SCV000924868 uncertain significance not provided 2016-04-05 no assertion criteria provided provider interpretation

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