Submissions for variant NM_001267550.2(TTN):c.100417G>A (p.Gly33473Ser)

gnomAD frequency: 0.00013  dbSNP: rs397517783

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040896	SCV000064587	uncertain significance	not specified	2015-09-08	criteria provided, single submitter	clinical testing	The p.Gly30905Ser variant in TTN has been identified by our laboratory in 1 mixe d race individual with HCM. This variant has been identified in 4/66100 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs397517783). Computational prediction tools and conservation anal ysis do not provide strong support for or against an impact to the protein. In s ummary, the clinical significance of the p.Gly30905Ser variant is uncertain.
Eurofins Ntd Llc (ga)	RCV000725603	SCV000338093	uncertain significance	not provided	2015-12-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381321	SCV002674401	likely benign	Cardiovascular phenotype	2020-05-27	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Athena Diagnostics	RCV000725603	SCV002770633	uncertain significance	not provided	2022-08-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477125	SCV002776414	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	2021-10-20	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000725603	SCV003826730	uncertain significance	not provided	2022-04-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040896	SCV003928666	uncertain significance	not specified	2024-12-09	criteria provided, single submitter	clinical testing	Variant summary: TTN c.92713G>A (p.Gly30905Ser) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.9e-05 in 1583086 control chromosomes, predominantly at a frequency of 0.00049 within the Non-Finnish European subpopulation in the gnomAD database. 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.92713G>A in individuals affected with TTN-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 47627). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000725603	SCV004150196	uncertain significance	not provided	2023-02-01	criteria provided, single submitter	clinical testing	TTN: PM2
Breakthrough Genomics, Breakthrough Genomics	RCV000725603	SCV005188101	uncertain significance	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000725603	SCV005412977	uncertain significance	not provided	2023-11-27	criteria provided, single submitter	clinical testing