Submissions for variant NM_001267550.2(TTN):c.92699A>G (p.Asn30900Ser)

gnomAD frequency: 0.00015  dbSNP: rs186234393

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000461639	SCV000237769	likely benign	not provided	2020-07-14	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27066551)
Ambry Genetics	RCV000249807	SCV000319715	likely benign	Cardiovascular phenotype	2019-09-23	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.
Eurofins Ntd Llc (ga)	RCV000373149	SCV000342637	likely benign	not specified	2016-06-07	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000338023	SCV000420823	uncertain significance	Myopathy, myofibrillar, 9, with early respiratory failure	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397369	SCV000420824	uncertain significance	Limb-girdle muscular dystrophy, recessive	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000278867	SCV000420825	uncertain significance	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000336224	SCV000420826	uncertain significance	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000397381	SCV000420827	uncertain significance	Early-onset myopathy with fatal cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000315107	SCV000420828	uncertain significance	Tibial muscular dystrophy	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084202	SCV000555295	likely benign	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2025-02-02	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000768859	SCV000900232	benign	Cardiomyopathy	2020-06-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000461639	SCV001152656	uncertain significance	not provided	2016-05-01	criteria provided, single submitter	clinical testing
Genetics and Genomics Program, Sidra Medicine	RCV001293190	SCV001434188	likely benign	Primary dilated cardiomyopathy		criteria provided, single submitter	research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000373149	SCV005886994	likely benign	not specified	2025-01-28	criteria provided, single submitter	clinical testing	Variant summary: TTN c.84995A>G (p.Asn28332Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 248822 control chromosomes, predominantly at a frequency of 0.0043 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 11.013 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Autosomal Recessive Titinopathy phenotype (0.00039). c.84995A>G has been reported in the literature in at-least one individual affected with Neuromuscular disorder (example: Tian_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Autosomal Recessive Titinopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27066551). ClinVar contains an entry for this variant (Variation ID: 202990). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004537559	SCV004741101	likely benign	TTN-related disorder	2024-02-15	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).