Submissions for variant NM_001267550.2(TTN):c.81302G>T (p.Gly27101Val)

gnomAD frequency: 0.00032  dbSNP: rs201490050

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000184873	SCV000701348	uncertain significance	not provided	2017-04-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619230	SCV000736938	likely benign	Cardiovascular phenotype	2020-01-16	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086421	SCV000765375	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2024-12-12	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001706158	SCV001879708	likely benign	not specified	2021-03-22	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000184873	SCV003820321	uncertain significance	not provided	2019-01-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000184873	SCV004150265	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000184873	SCV004225804	uncertain significance	not provided	2022-10-26	criteria provided, single submitter	clinical testing	BS1
GeneDx	RCV000184873	SCV000237612	not provided	not provided	2014-04-14	no assertion provided	clinical testing	Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM-CRDM panel(s).
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678759	SCV000804938	uncertain significance	Left ventricular hypertrophy	2015-11-04	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004537555	SCV004716584	uncertain significance	TTN-related disorder	2023-10-28	no assertion criteria provided	clinical testing	The TTN c.81302G>T variant is predicted to result in the amino acid substitution p.Gly27101Val. This variant was reported in an individual with dilated cardiomyopathy (Table S3, Mazzarotto et al. 2020. PubMed ID: 31983221). This variant is reported in 0.11% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179429557-C-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.