Submissions for variant NM_001267550.2(TTN):c.88972A>G (p.Ile29658Val)

gnomAD frequency: 0.00024  dbSNP: rs200193877

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154900	SCV000204582	likely benign	not specified	2013-08-02	criteria provided, single submitter	clinical testing	Ile27090Val in exon 282 of TTN: This variant is not expected to have clinical si gnificance due to a lack of evolutionary conservation. Multiple mammals have a v aline (Val) at this position despite high nearby amino acid conservation. This v ariant has also been identified in 4/8298 European American chromosomes by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs200193 877).
GeneDx	RCV000710279	SCV000237712	likely benign	not provided	2021-05-05	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23861362, 26395554)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230724	SCV000286897	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2017-11-06	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000710279	SCV000616168	uncertain significance	not provided	2017-06-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000710279	SCV000703188	uncertain significance	not provided	2017-03-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621138	SCV000735542	likely benign	Cardiovascular phenotype	2018-01-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000710279	SCV001502340	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	TTN: BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154900	SCV001774760	uncertain significance	not specified	2021-07-12	criteria provided, single submitter	clinical testing	Variant summary: TTN c.81268A>G (p.Ile27090Val) results in a conservative amino acid change located in the A-band (https://www.cardiodb.org/) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 247560 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (0.00017 vs 0.00039), allowing no conclusion about variant significance. c.81268A>G has been reported in the literature in an individual affected with malformation of cortical development (MCD; Zillhardt_2016). This report however, does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=4) or likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV000710279	SCV003824260	uncertain significance	not provided	2020-09-07	criteria provided, single submitter	clinical testing
Génétique et pathophysiologie de maladies neurodéveloppementales et épileptogènes, Institut de génétique et de biologie moléculaire et cellulaire	RCV000201380	SCV000239996	benign	Abnormality of neuronal migration	2014-10-31	no assertion criteria provided	clinical testing