Submissions for variant NM_001267550.2(TTN):c.97417C>T (p.Arg32473Cys)

gnomAD frequency: 0.00001  dbSNP: rs371924787

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000622011	SCV000737340	uncertain significance	Cardiovascular phenotype	2017-12-12	criteria provided, single submitter	clinical testing	The p.R23408C variant (also known as c.70222C>T), located in coding exon 176 of the TTN gene, results from a C to T substitution at nucleotide position 70222. The arginine at codon 23408 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and unknown by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000642764	SCV000764451	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2018-11-06	criteria provided, single submitter	clinical testing	This sequence change replaces arginine with cysteine at codon 32473 of the TTN protein (p.Arg32473Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). 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. This variant identified in the TTN gene is located in the M band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. In summary, this variant is a novel missense change with unknown impact on protein function. Missense variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders. However, the available evidence is currently insufficient to determine this variant’s role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV001529788	SCV002541913	uncertain significance	not provided	2021-09-13	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529788	SCV001743863	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529788	SCV001958388	uncertain significance	not provided		no assertion criteria provided	clinical testing