ClinVar Miner

Submissions for variant NM_003319.4(TTN):c.80585_80595delinsTGAAAGAAAAA (p.Glu26862_Trp26865delinsValLysGluLys) (rs281864927)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000406890 SCV000340098 pathogenic not provided 2018-09-11 criteria provided, single submitter clinical testing
Invitae RCV000700718 SCV000829486 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2019-12-23 criteria provided, single submitter clinical testing This variant, c.107780_107790delinsTGAAAGAAAAA, is a complex sequence change that results in the alteration of 4 amino acids of the TTN protein (p.Glu35927_Trp35930delinsValLysGluLys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to segregate with autosomal dominant tibial muscular dystrophy and autosomal recessive limb-girdle muscular dystrophy in many families (PMID: 12145747, 24395473, 15728284). This variant is considered a founder mutation for TTN-related disorders in the Finnish population and is also known as the FINmaj mutation in the literature. ClinVar contains an entry for this variant (Variation ID: 12652). This variant identified in the TTN gene is located in the M band of the resulting protein (PMID: 25589632). Experimental studies have shown that this variant reduces protein expression, causes protein misfolding, and increases protein aggregation and degradation (PMID: 25739468, 24395473). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000406890 SCV000927484 pathogenic not provided 2017-11-29 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000406890 SCV001146312 pathogenic not provided 2018-12-24 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/248952 chr). Found in at least one symptomatic patient. Statistically associated with disease in multiple families. (p < 0.05)
OMIM RCV000013487 SCV000033734 pathogenic Tibial muscular dystrophy 2010-09-24 no assertion criteria provided literature only
GeneReviews RCV000013487 SCV000054695 pathogenic Tibial muscular dystrophy 2019-12-19 no assertion criteria provided literature only
OMIM RCV000013488 SCV000809049 pathogenic Limb-girdle muscular dystrophy, type 2J 2010-09-24 no assertion criteria provided literature only

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