ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.67104A>C (p.Lys22368Asn) (rs727503577)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000152246 SCV000201055 uncertain significance not specified 2014-02-13 criteria provided, single submitter clinical testing The Lys19800Asn variant in TTN has been identified by our laboratory in 1 adult with HCM and in 1 infant with HCM, LVNC, CHD, and other syndromic features (LMM unpublished data). This variant has not been identified in large and broad Europ ean American and African American populations by the NHLBI Exome Sequencing Proj ect (http://evs.gs.washington.edu/EVS), though it may be present in other popula tions. Lysine (Lys) at position 19800 is not conserved in mammals, suggesting th at a change at this position may be tolerated. Additional computational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not prov ide strong support for or against an impact to the protein. Additional studies a re needed to fully assess the clinical significance of this variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724292 SCV000228413 uncertain significance not provided 2014-12-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000343431 SCV000422137 uncertain significance Myopathy, early-onset, with fatal cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000405984 SCV000422138 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000308543 SCV000422139 uncertain significance Myopathy, myofibrillar, 9, with early respiratory failure 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000365300 SCV000422140 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000402985 SCV000422141 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000311951 SCV000422142 uncertain significance Distal myopathy Markesbery-Griggs type 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000724292 SCV001004190 likely benign not provided 2018-03-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000152246 SCV001157943 uncertain significance not specified 2018-10-28 criteria provided, single submitter clinical testing The TTN c.59400A>C; p.Lys19800Asn variant (rs727503577; ClinVar Variation ID: 165883) 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 p.Lys19800Asn variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28.

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