ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.842+1G>C (rs111377893)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458092 SCV000541930 likely pathogenic Familial hypertrophic cardiomyopathy 2 2016-09-05 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 15 of the TNNT2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TNNT2-related disease. ClinVar contains an entry for this variant (Variation ID: 181649). A different variant affecting this nucleotide has been reported to segregate with hypertrophic cardiomyopathy in a large family and has a dominant-negative effect on TNNT2 function (PMID: 8205619, 8958207, 9637714, 10529204, 21245263, 27036851), indicating that this nucleotide may be crucial for normal TNNT2 activity. This also suggests that other variants affecting this nucleotide might have the same deleterious effect on protein activity since they could lead to a similar splicing defect. In summary, this is a rare splice variant at a position previously linked to TNNT2-related disease. In the absence of confirmed functional or segregating data, at this time this variant has been classified as Likely Pathogenic.

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