ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.95195C>T (p.Pro31732Leu) (rs753334568)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684823 SCV000543162 pathogenic Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-08-10 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 31732 of the TTN protein (p.Pro31732Leu). There is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs753334568, ExAC 0.006%). This variant has been reported in individuals and families affected with hereditary myopathy with early respiratory failure (HMERF) (PMID: 23486992, 22526018, 25500009, 23606733). It has been observed in both the heterozygous and homozygous state in affected individuals and is associated with a more severe phenotype when homozygous. It has also been observed in the heterozygous state in unaffected relatives, suggesting that it is not completely penetrant or acts in a semi-dominant manner (PMID: 23606733). In one individual, this variant was shown to arise de novo (PMID: 25500009). This variant is also known as c.90272C>T (p.Pro30091Leu) and c.68576C>T (p.Pro22859Leu) in the literature. ClinVar contains an entry for this variant (Variation ID: 132137). This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). Experimental studies have shown that this missense change impairs folding and solubility of the TTN protein (PMID: 24636144). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727672 SCV000854982 pathogenic not provided 2017-12-03 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000727672 SCV001248005 pathogenic not provided 2018-12-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000727672 SCV001446810 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneReviews RCV000119025 SCV000153727 pathogenic Myopathy, myofibrillar, 9, with early respiratory failure 2020-03-16 no assertion criteria provided literature only

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