ClinVar Miner

Submissions for variant NM_213674.1(TPM2):c.412_414GAG[1] (p.Glu139del) (rs199476153)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000500415 SCV000597527 pathogenic Nemaline myopathy 4 2016-04-28 criteria provided, single submitter clinical testing
Invitae RCV000532873 SCV000630170 pathogenic Distal arthrogryposis type 1A 2017-02-07 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 4 of the TPM2 mRNA (c.415_417delGAG). This leads to the deletion of 1 amino acid residue in the TPM2 protein (p.Glu139del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (rs199476153, ExAC no frequency). This variant has been reported in multiple unrelated individuals affected with cap myopathy and nemaline myopathy (PMID: 17434307, 23015096, 24692096, 25127990), including several affected individuals where it arose de novo (PMID: 19345583, 24507666). ClinVar contains an entry for this variant (Variation ID: 12465). Experimental studies have shown that this in-frame deletion causes increased calcium sensitivity and inhibits myosin binding (PMID: 23886664, 25978979). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013281 SCV000033528 pathogenic Cap myopathy 2 2009-05-01 no assertion criteria provided literature only
TPM2 homepage - Leiden Muscular Dystrophy pages RCV000128684 SCV000172324 not provided not provided no assertion provided not provided

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