Submissions for variant NM_001267550.2(TTN):c.77093T>G (p.Val25698Gly)

gnomAD frequency: 0.00003  dbSNP: rs759278736

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000619043	SCV000736966	uncertain significance	Cardiovascular phenotype	2020-09-09	criteria provided, single submitter	clinical testing	The p.V16633G variant (also known as c.49898T>G), located in coding exon 153 of the TTN gene, results from a T to G substitution at nucleotide position 49898. The valine at codon 16633 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Athena Diagnostics	RCV000993482	SCV001146490	uncertain significance	not provided	2019-06-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000993482	SCV001795543	uncertain significance	not provided	2019-07-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483709	SCV002791589	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	2021-12-07	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000993482	SCV003826025	uncertain significance	not provided	2020-02-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003403426	SCV004122226	uncertain significance	not specified	2023-10-26	criteria provided, single submitter	clinical testing	Variant summary: TTN c.69389T>G (p.Val23130Gly) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248290 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.69389T>G in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J or Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.