Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000688344 | SCV000815950 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2021-06-13 | 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with LRSAM1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 176 of the LRSAM1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LRSAM1 protein. This variant also falls at the last nucleotide of exon 8 of the LRSAM1 coding sequence, which is part of the consensus splice site for this exon. |
| Illumina Laboratory Services, |
RCV000688344 | SCV001331877 | uncertain significance | Charcot-Marie-Tooth disease axonal type 2P | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |