Submissions for variant NM_001267550.2(TTN):c.96016G>A (p.Val32006Met)

gnomAD frequency: 0.00035  dbSNP: rs191786700

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000643238	SCV000237816	likely benign	not provided	2021-06-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26582918)
Eurofins Ntd Llc (ga)	RCV000327957	SCV000343945	likely benign	not specified	2016-08-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086209	SCV000764925	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2025-01-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000643238	SCV001146546	likely benign	not provided	2018-11-14	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000643238	SCV002049745	uncertain significance	not provided	2024-09-12	criteria provided, single submitter	clinical testing	The TTN c.96016G>A; p.Val32006Met variant (rs191786700; ClinVar Variation ID: 203019) is rare in the general population (<0.2% 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.Val32006Met variant cannot be determined with certainty.
Ambry Genetics	RCV002362966	SCV002662918	likely benign	Cardiovascular phenotype	2020-01-31	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.
Revvity Omics, Revvity	RCV000643238	SCV003822353	uncertain significance	not provided	2020-06-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000327957	SCV005423397	likely benign	not specified	2024-10-04	criteria provided, single submitter	clinical testing	Variant summary: TTN c.88312G>A (p.Val29438Met) results in a conservative amino acid change located in the A-band region of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 1605752 control chromosomes in the gnomAD database (v4.1 dataset), including one homozygote. The variant was predominantly reported within the African or African-American subpopulation at a frequency of 0.0012, implying that it might be a benign polymorphism. To our knowledge, no occurrence of c.88312G>A in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 203019). Based on the evidence outlined above, the variant was classified as likely benign.
Clinical Genetics, Academic Medical Center	RCV000643238	SCV001924648	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000643238	SCV001953223	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000643238	SCV001978090	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000643238	SCV002036700	likely benign	not provided		no assertion criteria provided	clinical testing