ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)

gnomAD frequency: 0.00010  dbSNP: rs147580120
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172464 SCV000055103 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000642748 SCV000764435 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2017-09-04 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 2309 of the TTN protein (p.Asn2309Lys). There is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs147580120, ExAC 0.07%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 192073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
GeneDx RCV000172464 SCV001771985 likely benign not provided 2020-04-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002362887 SCV002662491 uncertain significance Cardiovascular phenotype 2019-06-18 criteria provided, single submitter clinical testing The p.N2263K variant (also known as c.6789T>A), located in coding exon 28 of the TTN gene, results from a T to A substitution at nucleotide position 6789. The asparagine at codon 2263 is replaced by lysine, an amino acid with similar properties. This alteration has been reported (as NM_133378.4:c.6927T>A p.N2309K) as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is not 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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