ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.815A>C (p.Glu272Ala)

dbSNP: rs727503519
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Total submissions: 2
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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 RCV000152123 SCV000200811 uncertain significance not specified 2014-12-04 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Glu272Ala variant in TPM1 has not been previously reported in individuals with cardiomyop athy or in large population studies. Glutamic acid at position 272 is highly con served in evolution and the change to alanine (Ala) was predicted to be pathogen ic using a computational tool clinically validated by our laboratory. This tool' s pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011) . In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Glu272Ala variant is uncertain.
Invitae RCV001850075 SCV002134796 uncertain significance Hypertrophic cardiomyopathy 2021-07-04 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with alanine at codon 272 of the TPM1 protein (p.Glu272Ala). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with dilated cardiomyopathy (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 165575). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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