ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.318G>C (p.Lys106Asn)

dbSNP: rs750350912
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001190937 SCV001358580 uncertain significance Cardiomyopathy 2019-07-30 criteria provided, single submitter clinical testing This missense variant replaces lysine with asparagine at codon 106 of the TNNI3 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 5/249462 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001297941 SCV001486980 uncertain significance Hypertrophic cardiomyopathy 2020-10-15 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 24793961). This variant is present in population databases (rs750350912, ExAC 0.008%). This sequence change replaces lysine with asparagine at codon 106 of the TNNI3 protein (p.Lys106Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine.
Ambry Genetics RCV003293969 SCV004001496 uncertain significance Cardiovascular phenotype 2023-03-29 criteria provided, single submitter clinical testing The p.K106N variant (also known as c.318G>C), located in coding exon 6 of the TNNI3 gene, results from a G to C substitution at nucleotide position 318. The lysine at codon 106 is replaced by asparagine, an amino acid with similar properties. This alteration has been reported in association with hypertrophic cardiomyopathy (HCM) (Bos JM et al. Mayo Clin Proc, 2014 Jun;89:727-37). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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