ClinVar Miner

Submissions for variant NM_003283.6(TNNT1):c.538G>T (p.Glu180Ter) (rs80358249)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000020554 SCV000763599 pathogenic Nemaline myopathy 5 2017-12-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu180*) in the TNNT1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs80358249, ExAC 0.002%). This variant has been reported to segregate with Amish nemaline myopathy in a family and is considered a founder mutation in the Amish population (PMID: 10952871). ClinVar contains an entry for this variant (Variation ID: 12440). Experimental studies have shown that this nonsense change impairs tropomyosin binding and results in absent troponin T protein in muscle cells (PMID: 27429059, 12732643, 15665378). Loss-of-function variants in TNNT1 are known to be pathogenic (PMID: 10952871, 24689076, 25430424). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000020554 SCV000033500 pathogenic Nemaline myopathy 5 2005-04-08 no assertion criteria provided literature only
GeneReviews RCV000020554 SCV000041024 pathologic Nemaline myopathy 5 2012-03-15 no assertion criteria provided curation Converted during submission to Pathogenic.
Leiden Muscular Dystrophy (TNNT1) RCV000024549 SCV000045853 not provided not provided 2012-03-18 no assertion provided curation

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