Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000534855 | SCV000652077 | uncertain significance | Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease, dominant intermediate E | 2019-04-08 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine with aspartic acid at codon 50 of the INF2 protein (p.Tyr50Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Charcot-Marie-Tooth disease and focal segmental glomerulosclerosis (PMID: 28780565, Invitae). ClinVar contains an entry for this variant (Variation ID: 472837). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |