ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.131C>G (p.Ser44Trp) (rs730881085)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159256 SCV000209202 likely pathogenic not provided 2011-11-15 criteria provided, single submitter clinical testing The Ser44Trp variant in the TNNI3 gene has not been reported previously as a disease-causing mutation or as a benign polymorphism, to our knowledge. Ser44Trp results in a non-conservative amino acid substitution of a neutral, polar Serine with a non-polar Tryptophan at a position that is conserved throughout evolution. Three in silico analysis programs predict Ser44Trp is probably damaging to protein structure/function. Although there is one missense mutation nearby (Lys36Gln) that has been reported in association with cardiomyopathy, there are very few reported missense mutations in the N-terminus of TNNI3. Finally, Ser44Trp was not detected in up to 200 control alleles from Caucasian individuals tested at GeneDx, indicating it is not a common variant in this population. The variant is found in DCM panel(s).
Invitae RCV001058132 SCV001222678 uncertain significance Hypertrophic cardiomyopathy 2020-10-04 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 44 of the TNNI3 protein (p.Ser44Trp). The serine residue is highly conserved and there is a large physicochemical difference between serine and tryptophan. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 181597). 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: Possibly Damaging; Align-GVGD: Class C1). 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. 5

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