Submissions for variant NM_001267550.2(TTN):c.68195C>T (p.Ser22732Leu)

gnomAD frequency: 0.00001  dbSNP: rs727505352

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726470	SCV000344909	uncertain significance	not provided	2016-09-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000339197	SCV000719436	likely benign	not specified	2017-12-07	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	RCV000642960	SCV000764647	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-01	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852819	SCV000995548	likely benign	Cardiomyopathy	2018-12-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000339197	SCV002556131	uncertain significance	not specified	2022-06-23	criteria provided, single submitter	clinical testing	Variant summary: TTN c.60491C>T (p.Ser20164Leu) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 247480 control chromosomes. c.60491C>T has been reported in the literature in individuals affected with sudden death with rare idiopathic disease cases or in stillbirth cases without chromosomal abnormalities, without strong evidence for causality (Sahlin_2019, Salfati_2019). These reports do not provide unequivocal conclusions about association of the variant with Limb-Girdle Muscular Dystrophy, Type 2J. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two submitters classify the variant as VUS while two classify as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV000726470	SCV003825610	uncertain significance	not provided	2020-02-24	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000726470	SCV001797820	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000726470	SCV001954067	likely benign	not provided		no assertion criteria provided	clinical testing