ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn) (rs281864928)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001319595 SCV001510348 uncertain significance Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-07-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with asparagine at codon 35947 of the TTN protein (p.Ile35947Asn). There is a large physicochemical difference between isoleucine and asparagine. This variant is present in population databases (rs281864928, ExAC 0.002%). This variant has been observed in individual(s) with clinical features of tibial muscular dystrophy (PMID: 12891679, 27796757). It has also been observed to segregate with disease in related individuals. This variant is also described as ATT>AAT change at position 293,329 in Mex6, I57N, p.I34306N, or p.I33379N in the literature. ClinVar contains an entry for this variant (Variation ID: 12654). This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). This variant has been reported not to substantially affect TTN protein function (PMID: 25877298 25739468). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000013490 SCV000033737 pathogenic Tibial muscular dystrophy 2003-08-01 no assertion criteria provided literature only
GeneReviews RCV000013490 SCV000054697 pathogenic Tibial muscular dystrophy 2019-12-19 no assertion criteria provided literature only
Institute of Human Genetics, Klinikum rechts der Isar RCV000013490 SCV001149973 pathogenic Tibial muscular dystrophy 2020-02-12 no assertion criteria provided clinical testing

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