Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000613281 | SCV000727632 | likely benign | not specified | 2018-02-22 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV002066603 | SCV002422049 | likely benign | Hypertrophic cardiomyopathy | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000613281 | SCV002600848 | benign | not specified | 2022-10-31 | criteria provided, single submitter | clinical testing | Variant summary: TNNI3 c.282+16_282+17delinsTT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 150826 control chromosomes, reported as two variants: 19-55156184-T-A and 19-55156185-C-A both found in 20 individuals in the gnomAD database (v3.1). Found predominantly at a frequency of 0.00044 within the African or African-American subpopulation in gnomAD, the observed variant frequency within these control individuals is approximately 3.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in TNNI3 causing Cardiomyopathy phenotype (0.00044 vs 0.00013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.282+16_282+17delinsTT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |