Submissions for variant NM_001267550.2(TTN):c.22091G>A (p.Arg7364Gln)

gnomAD frequency: 0.00011  dbSNP: rs200128066

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000595955	SCV000703810	uncertain significance	not provided	2016-12-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000595955	SCV003824101	uncertain significance	not provided	2023-05-26	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000595955	SCV001553429	uncertain significance	not provided		no assertion criteria provided	clinical testing	The TTN p.Arg6120Gln variant was not identified in the literature but was identified in dbSNP (ID: rs200128066) and ClinVar (classified as uncertain significance by EGL Genetic Diagnostics). The variant was identified in control databases in 13 of 279770 chromosomes at a frequency of 0.00004647 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 2 of 24180 chromosomes (freq: 0.000083), European (non-Finnish) in 10 of 127912 chromosomes (freq: 0.000078) and Latino in 1 of 35270 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The p.Arg6120 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000595955	SCV001977820	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000595955	SCV001978577	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000595955	SCV001980447	uncertain significance	not provided		no assertion criteria provided	clinical testing