Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001378935 | SCV001576636 | likely pathogenic | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2022-10-13 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with clinical features of tibial muscular dystrophy (PMID: 12145747; Invitae). It has also been observed to segregate with disease in related individuals. 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. 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). Experimental studies have shown that this missense change affects TTN function (PMID: 25739468). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 12653). This variant is also known as Leu>Pro mutation at position 293357 and L66P. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 35956 of the TTN protein (p.Leu35956Pro). |
| Revvity Omics, |
RCV001781256 | SCV002021537 | likely pathogenic | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001781256 | SCV004035616 | likely pathogenic | not provided | 2023-09-13 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest that when this variant is transfected in E.coli, there is decreased expression compared to wild type, as well as misfolding at all temperatures impairing M10 binding properties (Rudloff et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Located in the M-line region of TTN; Also known as the French variant, L66P, and L33388P; This variant is associated with the following publications: (PMID: 25877298, 27854229, 12145747, 25739468) |
| OMIM | RCV000013489 | SCV000033736 | pathogenic | Tibial muscular dystrophy | 2002-09-01 | no assertion criteria provided | literature only | |
| Gene |
RCV000013489 | SCV000054698 | not provided | Tibial muscular dystrophy | no assertion provided | literature only |