ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.79C>G (p.Arg27Gly) (rs1555864366)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000606248 SCV000713222 uncertain significance not specified 2018-10-16 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg27Gly variant in TNNI3 was identified in one individual with infantile onset DCM and s egregated with disease in 3 affected family members (LMM data). It was absent fr om large population studies. Computational prediction tools and conservation ana lysis do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical signi ficance of the p.Arg27Gly variant is uncertain. ACMG/AMP Criteria applied: PM2; PP1.
Invitae RCV000800634 SCV000940363 uncertain significance Hypertrophic cardiomyopathy 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 27 of the TNNI3 protein (p.Arg27Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TNNI3-related disease. ClinVar contains an entry for this variant (Variation ID: 505803). 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 C0"). 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.

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