Submissions for variant NM_001267550.2(TTN):c.66590G>A (p.Arg22197Gln)

gnomAD frequency: 0.00014  dbSNP: rs374656017

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152249	SCV000201063	uncertain significance	not specified	2013-04-03	criteria provided, single submitter	clinical testing	The Arg19629Gln variant in TTN has not been reported in the literature nor previ ously identified by our laboratory. This variant has been identified in 1/3960 A frican American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS/). Computational analyses (biochemical amino acid properties , conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support fo r or against an impact to the protein. Additional information is needed to fully assess the clinical significance of this variant.
Eurofins Ntd Llc (ga)	RCV000724309	SCV000228409	uncertain significance	not provided	2014-12-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000724309	SCV000237442	likely benign	not provided	2020-02-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242806	SCV000320463	uncertain significance	Cardiovascular phenotype	2015-11-20	criteria provided, single submitter	clinical testing	The p.R13132Q variant (also known as c.39395G>A), located in coding exon 143 of the TTN gene, results from a G to A substitution at nucleotide position 39395. The arginine at codon 13132 is replaced by glutamine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs374656017. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.01% (1/12236) total alleles studied, having been observed in 0.03% (1/3960) African American alleles. 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 variant remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000724309	SCV001249863	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000724309	SCV003827427	uncertain significance	not provided	2023-04-27	criteria provided, single submitter	clinical testing