Submissions for variant NM_001267550.2(TTN):c.98893G>C (p.Asp32965His)

dbSNP: rs186405108

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000172176	SCV000051100	uncertain significance	not provided	2013-06-24	criteria provided, single submitter	research
GeneDx	RCV000172176	SCV000237860	likely benign	not provided	2020-08-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204075	SCV000262241	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-08-25	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000172176	SCV000338317	uncertain significance	not provided	2016-01-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619992	SCV000737090	likely benign	Cardiovascular phenotype	2019-06-24	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	RCV001804904	SCV002051299	uncertain significance	not specified	2021-12-20	criteria provided, single submitter	clinical testing	Variant summary: TTN c.91189G>C (p.Asp30397His) results in a non-conservative amino acid change located in the A-band: Fibronectin type-III 128 domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00021 in 248670 control chromosomes, predominantly at a frequency of 0.00039 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00021 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.91189G>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters have assessed the variant since 2014: two classified the variant as of uncertain significance and two as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV000172176	SCV003823564	uncertain significance	not provided	2021-10-05	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150038	SCV003838512	likely benign	Cardiomyopathy	2021-08-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000172176	SCV005436215	uncertain significance	not provided	2024-09-01	criteria provided, single submitter	clinical testing