ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.148C>A (p.Leu50Ile) (rs1060501866)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464388 SCV000547696 uncertain significance Hypertrophic cardiomyopathy 2016-10-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with isoleucine at codon 50 of the TPM1 protein (p.Leu50Ile). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TPM1-related disease. 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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