Submissions for variant NM_001267550.2(TTN):c.99946G>A (p.Ala33316Thr)

gnomAD frequency: 0.00011  dbSNP: rs374295768

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727859	SCV000237875	likely benign	not provided	2021-02-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001085795	SCV000555616	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727859	SCV000855326	uncertain significance	not provided	2018-08-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381616	SCV002672747	likely benign	Cardiovascular phenotype	2018-10-29	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004525889	SCV005039499	benign	not specified	2024-03-11	criteria provided, single submitter	clinical testing	Variant summary: TTN c.92242G>A (p.Ala30748Thr) results in a non-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 0.00014 in 1606638 control chromosomes, predominantly at a frequency of 0.001 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.92242G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 203051). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV004539727	SCV004769916	likely benign	TTN-related disorder	2021-02-10	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).