Submissions for variant NM_001267550.2(TTN):c.63272_63298dup (p.Asp21091_Tyr21099dup)

dbSNP: rs750904641

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000824724	SCV000344564	uncertain significance	not provided	2016-09-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000263563	SCV000572587	uncertain significance	not specified	2017-07-31	criteria provided, single submitter	clinical testing	A variant of unknown significance has been identified in the TNN gene. The c.55568_55594dup27 variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.55568_55594dup27 variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.55568_55594dup27 variant results in an in-frame duplication of nine amnio acid residues, denoted p.D18523_Y18531dup. This duplication occurs at a position that is conserved across species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics	RCV002450830	SCV002616585	uncertain significance	Cardiovascular phenotype	2021-03-27	criteria provided, single submitter	clinical testing	The c.36077_36103dup27 variant (also known as p.D12026_Y12034dup), located in coding exon 132 of the TTN gene, results from an in-frame duplication of 27 nucleotides at nucleotide positions 36077 to 36103. This results in the duplication of 9 extra residues (DGGAPIIGY) between codons 12026 and 12034. This amino acid region is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002487279	SCV002785889	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-09-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000824724	SCV003819004	uncertain significance	not provided	2019-04-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000263563	SCV004240878	uncertain significance	not specified	2023-12-11	criteria provided, single submitter	clinical testing	Variant summary: TTN c.55568_55594dup27 (p.Asp18523_Tyr18531dup) results in an in-frame duplication that is predicted to duplicate 9 amino acids into the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 248092 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.55568_55594dup27 in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.