Submissions for variant NM_001267550.2(TTN):c.75458C>T (p.Ser25153Leu)

gnomAD frequency: 0.00006  dbSNP: rs368058280

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000501746	SCV000597688	uncertain significance	not specified	2016-08-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000501746	SCV001339101	uncertain significance	not specified	2020-03-10	criteria provided, single submitter	clinical testing	Variant summary: TTN c.67754C>T (p.Ser22585Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 9.6e-05 in 248728 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Cardiomyopathy (9.6e-05 vs 0.00063), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.67754C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV003139707	SCV003825459	uncertain significance	not provided	2019-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003139707	SCV004150281	likely benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	TTN: BP4, BS2