Submissions for variant NM_001267550.2(TTN):c.25563C>T (p.Gly8521=)

gnomAD frequency: 0.00009  dbSNP: rs556205722

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000155696	SCV000169644	benign	not specified	2014-04-29	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	RCV000155696	SCV000205406	likely benign	not specified	2013-05-03	criteria provided, single submitter	clinical testing	p.Gly7277Gly in exon 85 of TTN: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000231186	SCV000286528	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-07	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000155696	SCV001338621	likely benign	not specified	2020-04-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812063	SCV001474242	uncertain significance	not provided	2020-04-30	criteria provided, single submitter	clinical testing	The TTN c.25563C>T; p.Gly8521= variant (rs556205722), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 137843). This variant is found in the general population with an overall allele frequency of 0.01% (20/280072 alleles) in the Genome Aggregation Database. This is a synonymous variant in a weakly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by creating a novel cryptic donor splice site; however, RNA studies would be required to determine an effect on splicing. Even if used, the cryptic donor site would only be predicted to remove 26 amino acids and leave the remainder of the protein in-frame. However, due to limited information, the clinical significance of the c.25563C>T; p.Gly8521= variant is uncertain at this time.
Revvity Omics, Revvity	RCV001812063	SCV003824751	uncertain significance	not provided	2022-08-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001812063	SCV004183828	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	TTN: BP4, BP7