ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.240+1G>A (rs730881146)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159383 SCV000209329 pathogenic not provided 2013-10-30 criteria provided, single submitter clinical testing Although the c.240+1 G>A mutation has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge, this mutation destroys the canonical splice donor site in intron 2 and is predicted to cause abnormal gene splicing. The mutation is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Another splice site mutation in the TPM1 gene has been reported in association with HCM. Lastly, the c.240+1 G>A mutation 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. In summary, c.240+1 G>A in the TPM1 gene is interpreted as a disease-causing mutation. The variant is found in DCM-CRDM panel(s).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000214847 SCV000272534 uncertain significance not specified 2015-02-12 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The c.240+1G>A variant in TPM1 has not been previously reported in individuals with cardiomyopa thy and was absent from large population studies. This variant occurs in the inv ariant region (+/- 1,2) of the splice consensus sequence and is predicted to cau se altered splicing leading to an abnormal or absent protein. Despite the severi ty of the predicted impact it is unclear if this change causes disease because t his type of variant is very rare in this gene. In summary, while there is some s uspicion for a pathogenic role, the clinical significance of the c.240+1G>A vari ant is uncertain.

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