Submissions for variant NM_001267550.2(TTN):c.58658G>A (p.Arg19553Gln)

gnomAD frequency: 0.00001  dbSNP: rs543279513

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000696819	SCV000825398	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-02-21	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with glutamine at codon 19553 of the TTN protein (p.Arg19553Gln). There is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs543279513, ExAC 0.02%). This variant has not been reported in the literature in individuals with TTN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. 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.
Ambry Genetics	RCV002325397	SCV002610498	uncertain significance	Cardiovascular phenotype	2020-07-24	criteria provided, single submitter	clinical testing	The p.R10488Q variant (also known as c.31463G>A), located in coding exon 125 of the TTN gene, results from a G to A substitution at nucleotide position 31463. The arginine at codon 10488 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly 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.
CeGaT Center for Human Genetics Tuebingen	RCV003432741	SCV004152359	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	TTN: PM2, BP1, BP4