Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000034318 | SCV000813858 | pathogenic | Charcot-Marie-Tooth disease axonal type 2P | 2022-05-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 24 of the LRSAM1 gene. It does not directly change the encoded amino acid sequence of the LRSAM1 protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant Charcot-Marie-Tooth disease (PMID: 22781092, 28286897). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 41418). 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 LRSAM1 function (PMID: 29845787). 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 activation of a cryptic splice site and introduces a new termination codon (PMID: 22781092). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000034318 | SCV000058269 | pathogenic | Charcot-Marie-Tooth disease axonal type 2P | 2013-02-01 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000789359 | SCV000928714 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |