ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.14_16AGA[2] (p.Lys7del) (rs730881155)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159405 SCV000209351 uncertain significance not specified 2014-02-24 criteria provided, single submitter clinical testing The c.20_22delAGA variant in the TPM1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. c.20_22delAGA results in an in-frame deletion of a Lysine residue at codon 7, denoted p.Lys7del. In-frame deletions have not been repoted in the TPM1 gene in association with cardiomyopathy. With the clinical and molecular information available at this time, we cannot definitively determine if c.20_22delAGA is a disease-causing mutation or a rare benign variant.
Blueprint Genetics RCV000208256 SCV000264264 uncertain significance Left ventricular noncompaction cardiomyopathy 2015-06-05 criteria provided, single submitter clinical testing
Invitae RCV000545417 SCV000623797 uncertain significance Hypertrophic cardiomyopathy 2019-10-03 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 1 of the TPM1 mRNA (c.20_22delAGA). This leads to the deletion of 1 amino acid residue in the TPM1 protein (p.Lys7del) but otherwise preserves the integrity of the reading frame. 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. ClinVar contains an entry for this variant (Variation ID: 181682). The TPM1 and TPM2 genes code for different isoforms of tropomyosin and share a high amount of sequence homology (PMID: 27420374). The same variant c.20_22del (p.Lys7del) located in TPM2 has been determined to be pathogenic and is a recurrent variant in families affected with congenital myopathies (PMID: 25552303, 24692096, 23413262). However, the clinical significance of this variant in TPM1 has not been determined. In summary, this variant is a novel in-frame deletion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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