ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.107867T>C (p.Leu35956Pro) (rs267607156)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001378935 SCV001576636 likely pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-02-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 35956 of the TTN protein (p.Leu35956Pro). There is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of tibial muscular dystrophy (PMID: 12145747, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as Leu>Pro mutation at position 293357 and L66P in the literature. ClinVar contains an entry for this variant (Variation ID: 12653). 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 to affect TTN protein function (PMID: 25739468). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013489 SCV000033736 pathogenic Tibial muscular dystrophy 2002-09-01 no assertion criteria provided literature only
GeneReviews RCV000013489 SCV000054698 pathogenic Tibial muscular dystrophy 2019-12-19 no assertion criteria provided literature only

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