Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182362 | SCV000234681 | pathogenic | not provided | 2023-11-27 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28152038, 29861492, 25886484) |
| Labcorp Genetics |
RCV000229718 | SCV000291542 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln353*) in the LMNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). This variant is present in population databases (rs267607623, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with amyotrophy of the lower limbs, arrhythmia and cardiac hypofunction (PMID: 25886484). ClinVar contains an entry for this variant (Variation ID: 200939). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000247014 | SCV000319073 | pathogenic | Cardiovascular phenotype | 2018-04-11 | criteria provided, single submitter | clinical testing | The p.Q353* pathogenic mutation (also known as c.1057C>T), located in coding exon 6 of the LMNA gene, results from a C to T substitution at nucleotide position 1057. This changes the amino acid from a glutamine to a stop codon within coding exon 6. This mutation has been previously reported in a patient with an LMNA-associated laminopathy (Iwahara N et al. BMC Neurol. 2015;15:13). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Mayo Clinic Laboratories, |
RCV000182362 | SCV001715572 | pathogenic | not provided | 2019-09-25 | criteria provided, single submitter | clinical testing | PVS1, PM1, PM2 |
| Inherited Neuropathy Consortium | RCV000790003 | SCV000929392 | uncertain significance | Neuronopathy, distal hereditary motor, autosomal dominant | no assertion criteria provided | literature only |