Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000159240 | SCV000209186 | likely pathogenic | not provided | 2021-01-27 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar (ClinVar Variant ID# 36883; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000625703 | SCV000696596 | uncertain significance | not specified | 2016-10-27 | criteria provided, single submitter | clinical testing | Variant summary: The TNNI3 c.562G>A (p.Val188Met) variant involves the alteration of a conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this substitution. This variant is absent in 120606 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Mutations in nearby residues (Asn185Lys, Arg186Gln, Glu187Gly, Asp190Gly, Arg192Cys) are listed in HGMD as causative variants for cardiomyopathy or atrial fibrillation indicating the functional importance of this region of the protein. A clinical diagnostic laboratory classified this variant as likely pathogenic (without evidence to independently evaluate). Due to the absence of clinical information about variant carriers and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Invitae | RCV002513269 | SCV003033799 | uncertain significance | Hypertrophic cardiomyopathy | 2022-12-16 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 36883). This variant has not been reported in the literature in individuals affected with TNNI3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 188 of the TNNI3 protein (p.Val188Met). |
| Mayo Clinic Laboratories, |
RCV000159240 | SCV004225441 | uncertain significance | not provided | 2022-02-11 | criteria provided, single submitter | clinical testing | PP3, PM1, PM2_supporting |
| Ambry Genetics | RCV004018691 | SCV004968960 | uncertain significance | Cardiovascular phenotype | 2022-02-18 | criteria provided, single submitter | clinical testing | The c.562G>A (p.V188M) alteration is located in exon 8 (coding exon 8) of the TNNI3 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the valine (V) at amino acid position 188 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |