ClinVar Miner

Submissions for variant NM_133379.5(TTN):c.15302A>G (p.Glu5101Gly)

gnomAD frequency: 0.00024  dbSNP: rs142973956
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000218686 SCV000272856 uncertain significance not specified 2015-10-30 criteria provided, single submitter clinical testing The p.Glu5101Gly variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 21/66452 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s142973956). Computational prediction tools and conservation analysis are limite d or unavailable for this variant. In summary, the clinical significance of the p.Glu5101Gly variant is uncertain.
GeneDx RCV000997561 SCV001805061 likely benign not provided 2019-06-04 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000218686 SCV006067856 likely benign not specified 2025-04-09 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000997561 SCV001549992 uncertain significance not provided no assertion criteria provided clinical testing The TTN p.Glu5101Gly variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs142973956) and in ClinVar (classified as VUS by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine). The variant was also identified in control databases in 60 of 280694 chromosomes at a frequency of 0.000214 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 49 of 128338 chromosomes (freq: 0.000382), Other in 2 of 7130 chromosomes (freq: 0.000281), Latino in 6 of 35192 chromosomes (freq: 0.000171) and African in 3 of 24590 chromosomes (freq: 0.000122); it was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. Computational protein prediction programs (PolyPhen-2, MutationTaster, BLOSUM) provide inconsistent predictions regarding the impact to the protein. 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.

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