ClinVar Miner

Submissions for variant NM_001018005.2(TPM1):c.539A>G (p.Glu180Gly) (rs104894502)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159367 SCV000209313 pathogenic not provided 2017-04-17 criteria provided, single submitter clinical testing The Glu180Gly pathogenic variant in the TPM1 gene has been reported previously in association with HCM. Thierfelder et al. (1994) first reported Glu180Gly in two individuals with HCM in one family. Their two unaffected relatives did not harbor Glu180Gly, and the variant was not present in 200 control chromosomes. A mouse study demonstrated the Glu180Gly variant is severely disruptive to sarcomere function (Prabhakar R et al., 2001) and further studies report Gly180Gly causes changes to the actin-myosin interaction during the ATPase cycle (Rysev N et al., 2012). Another variant affecting the same residue (Glu180Val) and variants affecting nearby residues (Asp175Asn, Leu185Arg) have also been reported in association with HCM, further supporting the functional importance of this residue and this region of the protein. Furthermore, the Glu180Gly variant 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. Therefore, Glu180Gly in the TPM1 gene is interpreted as a pathogenic variant.
Leiden Muscular Dystrophy (TPM1) RCV000013271 SCV000045884 not provided Familial hypertrophic cardiomyopathy 3 2012-04-15 no assertion provided curation
OMIM RCV000013271 SCV000033518 pathogenic Familial hypertrophic cardiomyopathy 3 1994-06-03 no assertion criteria provided literature only

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