Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000558954 | SCV000636237 | pathogenic | Charcot-Marie-Tooth disease, type I | 2019-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with asparagine at codon 35 of the MPZ protein (p.Asp35Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Charcot-Marie-Tooth disease (CMT) and has been observed to segregate with CMT in affected families (PMID: 24444136, 20385006, 24053775). ClinVar contains an entry for this variant (Variation ID: 462790). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic. |
Institute of Human Genetics, |
RCV000995582 | SCV001149841 | pathogenic | Charcot-Marie-Tooth disease type 2I | 2019-10-09 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001093015 | SCV001249790 | pathogenic | not provided | 2020-01-01 | criteria provided, single submitter | clinical testing | |
Inherited Neuropathy Consortium | RCV000790058 | SCV000929448 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |