Submissions for variant NM_001267550.2(TTN):c.90691C>T (p.Pro30231Ser)

gnomAD frequency: 0.00012  dbSNP: rs373722546

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726510	SCV000701529	uncertain significance	not provided	2017-04-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000726510	SCV000729440	likely benign	not provided	2019-12-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000642932	SCV000764619	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-12-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002367999	SCV002660695	uncertain significance	Cardiovascular phenotype	2019-07-26	criteria provided, single submitter	clinical testing	The p.P21166S variant (also known as c.63496C>T), located in coding exon 162 of the TTN gene, results from a C to T substitution at nucleotide position 63496. The proline at codon 21166 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000726510	SCV003818361	uncertain significance	not provided	2021-08-09	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004526712	SCV005039201	uncertain significance	not specified	2024-03-22	criteria provided, single submitter	clinical testing	Variant summary: TTN c.82987C>T (p.Pro27663Ser) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 247906 control chromosomes. 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.82987C>T in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 497188). Based on the evidence outlined above, the variant was classified as uncertain significance.