Submissions for variant NM_001267550.2(TTN):c.50212G>A (p.Glu16738Lys)

gnomAD frequency: 0.00017  dbSNP: rs148018042

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000184587	SCV000237256	likely benign	not specified	2017-10-03	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.
Invitae	RCV000471332	SCV000542324	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-06	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000993449	SCV001146423	uncertain significance	not provided	2018-11-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000184587	SCV001572536	uncertain significance	not specified	2024-01-09	criteria provided, single submitter	clinical testing	Variant summary: TTN c.42508G>A (p.Glu14170Lys) results in a conservative amino acid change located in the A-Band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 247718 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00013 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.42508G>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: 202683). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV002444750	SCV002734215	likely benign	Cardiovascular phenotype	2020-06-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000993449	SCV003818491	uncertain significance	not provided	2021-04-22	criteria provided, single submitter	clinical testing
New York Genome Center	RCV003335182	SCV004046605	uncertain significance	Dilated cardiomyopathy 1G; Hypertrophic cardiomyopathy 9	2022-11-18	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003486749	SCV004239929	likely benign	Cardiomyopathy	2022-11-16	criteria provided, single submitter	clinical testing