Submissions for variant NM_001267550.2(TTN):c.3989G>A (p.Arg1330His)

gnomAD frequency: 0.00002  dbSNP: rs761402128

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000217473	SCV000237985	likely benign	not specified	2017-03-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217473	SCV000272658	uncertain significance	not specified	2017-08-04	criteria provided, single submitter	clinical testing	The p.Arg1330His variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 7/110486 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSN P rs761402128). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg1330His variant is uncertain.
Invitae	RCV000643782	SCV000765469	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-10-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362971	SCV002625882	uncertain significance	Cardiovascular phenotype	2020-09-10	criteria provided, single submitter	clinical testing	The p.R1284H variant (also known as c.3851G>A), located in coding exon 22 of the TTN gene, results from a G to A substitution at nucleotide position 3851. The arginine at codon 1284 is replaced by histidine, 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.
Revvity Omics, Revvity	RCV001706159	SCV003822252	uncertain significance	not provided	2021-04-29	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001706159	SCV001930388	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001706159	SCV001968242	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001706159	SCV001979744	uncertain significance	not provided		no assertion criteria provided	clinical testing