Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000015610 | SCV000595608 | pathogenic | Familial partial lipodystrophy, Dunnigan type | 2016-10-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003581575 | SCV004292924 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the LMNA gene. It does not directly change the encoded amino acid sequence of the LMNA protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in LMNA cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with partial lipodystrophy (PMID: 16636128, 31194872, 36397776). This variant is also known as IVS8+5G>C. ClinVar contains an entry for this variant (Variation ID: 66833). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects LMNA function (PMID: 16636128). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in intronic inclusion and introduces a premature termination codon (PMID: 16636128). The resulting mRNA is expected to undergo nonsense-mediated decay. 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 | RCV000015610 | SCV000035875 | pathogenic | Familial partial lipodystrophy, Dunnigan type | 2006-07-01 | no assertion criteria provided | literature only | |
Epithelial Biology; Institute of Medical Biology, |
RCV000057307 | SCV000088420 | not provided | not provided | no assertion provided | not provided |