Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463096 | SCV000544292 | likely pathogenic | Hereditary spastic paraplegia 2 | 2016-10-03 | criteria provided, single submitter | clinical testing | In summary, this variant is a rare missense that segregates with disease in a single family and is predicted to affect protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported to segregate with Pelizaeus-Merzbacher disease (PMD) in a single family (PMID: 24519770). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 47 of the PLP1 protein (p.Ile47Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |
Mayo Clinic Laboratories, |
RCV000681649 | SCV000809095 | likely pathogenic | Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2 | 2018-06-06 | criteria provided, single submitter | clinical testing | |
3billion | RCV003313955 | SCV004013846 | likely pathogenic | Pelizaeus-Merzbacher disease | criteria provided, single submitter | clinical testing | The missense variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 0.91). The same nucleotide change resulting in the same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000405941/PMID: 24519770). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |