Submissions for variant NM_001267550.2(TTN):c.107723T>C (p.Ile35908Thr)

gnomAD frequency: 0.00001  dbSNP: rs769141222

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001305110	SCV001494424	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 35908 of the TTN protein (p.Ile35908Thr). This variant is present in population databases (rs769141222, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007868). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Non-truncating variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001528552	SCV002074113	uncertain significance	not provided	2022-01-31	criteria provided, single submitter	clinical testing	Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31785789, 28135719, 28191890, 25533962)
Athena Diagnostics	RCV001528552	SCV002770566	uncertain significance	not provided	2021-07-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002499573	SCV002806836	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2021-12-28	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001528552	SCV003826605	uncertain significance	not provided	2020-09-02	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528552	SCV001740448	uncertain significance	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001528552	SCV001800060	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001528552	SCV001918265	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528552	SCV001972557	uncertain significance	not provided		no assertion criteria provided	clinical testing