Submissions for variant NM_001267550.2(TTN):c.32767A>C (p.Lys10923Gln)

gnomAD frequency: 0.00020  dbSNP: rs367720439

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155837	SCV000205548	uncertain significance	not specified	2015-01-14	criteria provided, single submitter	clinical testing	The p.Lys9679Gln variant in TTN has been identified by our laboratory in 1 adole scent with DCM, but has also been identified in 7/9768 African chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3 67720439). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predict ive enough to rule out pathogenicity. In summary, the clinical significance of t he p.Lys9679Gln variant is uncertain.
Fulgent Genetics, Fulgent Genetics	RCV000765582	SCV000896897	uncertain significance	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000184455	SCV001477124	likely benign	not provided	2019-09-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000155837	SCV002571826	likely benign	not specified	2024-10-21	criteria provided, single submitter	clinical testing	Variant summary: TTN c.29035A>C (p.Lys9679Gln) results in a conservative amino acid change located in the I-band domian of the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 248686 control chromosomes, predominantly at a frequency of 0.00078 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039). To our knowledge, no occurrence of c.29035A>C in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 179053). Based on the evidence outlined above, the variant was classified as likely benign.
Revvity Omics, Revvity	RCV000184455	SCV003822207	uncertain significance	not provided	2020-07-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000184455	SCV004225886	uncertain significance	not provided	2023-01-12	criteria provided, single submitter	clinical testing	BP4
GeneDx	RCV000184455	SCV000237089	not provided	not provided	2014-07-08	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 CARDIOMYOPATHY panel(s).