Submissions for variant NM_001267550.2(TTN):c.81869G>C (p.Gly27290Ala)

gnomAD frequency: 0.00010  dbSNP: rs200240728

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000472921	SCV000542307	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2016-05-22	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000727843	SCV000855287	uncertain significance	not provided	2017-12-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000727843	SCV001152718	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TTN: PM2
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001584130	SCV001821371	uncertain significance	not specified	2021-08-23	criteria provided, single submitter	clinical testing	Variant summary: TTN c.74165G>C (p.Gly24722Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.7e-05 in 248002 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (9.7e-05 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.74165G>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A co-occurrence with a pathogenic variant has been reported (MYBPC3 c.1504C>T, p.Arg502Trp; Internal testing). Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV000727843	SCV003826654	uncertain significance	not provided	2022-09-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925311	SCV004741852	uncertain significance	TTN-related condition	2023-12-16	criteria provided, single submitter	clinical testing	The TTN c.81869G>C variant is predicted to result in the amino acid substitution p.Gly27290Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.