ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.485_514del (p.Arg162_Ala171del) (rs1555863489)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000551389 SCV000623786 uncertain significance Hypertrophic cardiomyopathy 2017-03-16 criteria provided, single submitter clinical testing This sequence change deletes 30 nucleotides from exon 7 of the TNNI3 mRNA (c.485_514del30). This leads to the deletion of 10 amino acid residues in the TNNI3 protein (p.Arg162_Ala171del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TNNI3-related disease. Experimental studies and prediction algorithms are not available for this variant. Two missense substitutions at codons 162 and 170 (p.Arg162Gln and p.Arg170Trp) have been determined to be pathogenic (PMID: 15607392, 22876777, 20031618, 26440512). This suggests that these residues are critical for TNNI3 protein function and that their disruption due to this deletion at this position may also be pathogenic. In addition, this variant deletes part of the troponin C binding domain where other variants associated with restrictive and hypertrophic cardiomyopathy have been reported to occur (PMID: 26440512). In summary, this variant is an in-frame deletion that deletes amino acid residues important for TNNI3 protein function. However, the available genetic evidence is insufficient at this point to classify this variant conclusively. It has been classified as a Variant of Uncertain Significance.

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