Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617617 | SCV000738096 | likely benign | Cardiovascular phenotype | 2018-10-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Invitae | RCV001314765 | SCV001505311 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-07-26 | criteria provided, single submitter | clinical testing | 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. Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (PMID: 28679633). ClinVar contains an entry for this variant (Variation ID: 519479). This variant has not been reported in the literature in individuals affected with LMNA-related conditions. This variant is present in population databases (rs758848135, gnomAD 0.002%). This sequence change affects codon 160 of the LMNA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LMNA protein. |
| Color Diagnostics, |
RCV003532203 | SCV004359097 | uncertain significance | Cardiomyopathy | 2021-09-14 | criteria provided, single submitter | clinical testing | This synonymous variant does not change the amino acid sequence of the lamin A/C proteins. Splice site prediction tools and conservation analysis are inconclusive regarding the impact of this variant on RNA splicing. A functional study with minigene assay has shown that this variant alters mRNA splicing in vitro (PMID: 28679633). This variant has been reported in an individual affected with idiopathic ventricular fibrillation (PMID: 31453089). However, no abnormal splicing was detected in the RNA sample derived from this individual's peripheral blood cell, indicating that this variant has no impact on splicing in vivo and could not explain the observed phenotype. This variant has been identified in 2/232328 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |