Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000693004 | SCV000820857 | pathogenic | Charcot-Marie-Tooth disease type 2P | 2018-03-06 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 23 of the LRSAM1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs756880678, ExAC 0.002%). This variant has been reported to segregate in a autosomal recessive fashion with Charcot-Marie-Tooth disease type 2 in a family (PMID: 20865121). ClinVar contains an entry for this variant (Variation ID: 204301). Experimental studies have shown that this splice acceptor change results in aberrant splicing of the LRSAM1 gene, resulting in a frameshift and absence of protein in cultured patient cells (PMID: 20865121). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LRSAM1 are known to be pathogenic (PMID: 20865121). For these reasons, this variant has been classified as Pathogenic. |
Molecular Genetics Laboratory, |
RCV000192257 | SCV001336729 | pathogenic | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Gene |
RCV000192257 | SCV000239905 | pathogenic | Charcot-Marie-Tooth disease | 2015-04-30 | no assertion criteria provided | literature only | |
Inherited Neuropathy Consortium | RCV000192257 | SCV000928713 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |