ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.23065G>A (p.Asp7689Asn)

gnomAD frequency: 0.00005  dbSNP: rs727505052
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156481 SCV000206200 uncertain significance not specified 2014-05-01 criteria provided, single submitter clinical testing The Asp6445Asn variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity.Of n ote, 1 fish (Atlantic cod) carries an asparagine (Asn) at this position, raising the possibility that this change may be tolerated. In summary, the clinical sig nificance of the Asp6445Asn variant is uncertain.
GeneDx RCV000156481 SCV000238327 uncertain significance not specified 2014-02-21 criteria provided, single submitter 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).
Invitae RCV000461425 SCV000542314 uncertain significance Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J 2016-11-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764345 SCV000895364 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
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000156481 SCV001158187 uncertain significance not specified 2019-03-01 criteria provided, single submitter clinical testing The TTN c.19333G>A; p.Asp6445Asn variant (rs727505052; ClinVar Variation ID: 179685) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the Asp6445Asn variant cannot be determined with certainty.
Revvity Omics, Revvity RCV003137681 SCV003819190 uncertain significance not provided 2021-01-28 criteria provided, single submitter clinical testing

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