Submissions for variant NM_001267550.2(TTN):c.82103A>G (p.Asp27368Gly)

gnomAD frequency: 0.00014  dbSNP: rs145373396

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000040678	SCV000064369	uncertain significance	not specified	2012-07-10	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Asp24800Gly var iant in TTN has been identified in 1.5% (2/132) of Mexican American chromosomes from a broad population by the 1000 Genomes project (dbSNP rs145373396). This fr equency raises the possibility that the variant may be benign but is insufficien t to rule out a role in disease. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is neede d to fully assess its clinical significance.
Eurofins Ntd Llc (ga)	RCV000040678	SCV000228556	likely benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000040678	SCV000237624	likely benign	not specified	2017-04-07	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000456789	SCV000555423	benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2025-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619273	SCV000736789	likely benign	Cardiovascular phenotype	2018-09-06	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811298	SCV001471603	uncertain significance	not provided	2019-08-14	criteria provided, single submitter	clinical testing	The TTN c.82103A>G; p.Asp27368Gly variant (rs145373396) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p. Asp27368Gly variant cannot be determined with certainty.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000040678	SCV002500131	likely benign	not specified	2022-03-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001811298	SCV004225801	uncertain significance	not provided	2023-06-21	criteria provided, single submitter	clinical testing	BS1
PreventionGenetics, part of Exact Sciences	RCV004541182	SCV004785785	likely benign	TTN-related disorder	2020-10-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).