ClinVar Miner

Submissions for variant NM_000432.4(MYL2):c.421G>A (p.Ala141Thr)

dbSNP: rs727504559
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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, Mass General Brigham Personalized Medicine RCV000155724 SCV000205434 uncertain significance not specified 2013-05-03 criteria provided, single submitter clinical testing The Ala141Thr variant in MYL2 has not been reported in individuals with cardiomy opathy or in large population studies. Alanine (Ala) at position 141 is conserv ed across evolutionarily distinct species, increasing the likelihood that this c hange would not be tolerated. Other computational analyses (biochemical amino a cid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support fo r or against an impact to the protein. Additional information is needed to full y assess the clinical significance of the Ala141Thr variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000530339 SCV000638396 uncertain significance Hypertrophic cardiomyopathy 10 2023-08-27 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 178948). This missense change has been observed in individual(s) with clinical features of MYL2-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 141 of the MYL2 protein (p.Ala141Thr).
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852438 SCV000995130 uncertain significance Primary dilated cardiomyopathy 2019-05-08 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000530339 SCV001429498 uncertain significance Hypertrophic cardiomyopathy 10 2018-02-01 criteria provided, single submitter clinical testing
GeneDx RCV001555854 SCV001777334 uncertain significance not provided 2024-05-29 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30706179)

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