Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001045147 | SCV001208982 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2019-05-27 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with KIF1B-related conditions. This variant is present in population databases (rs779559577, ExAC 0.004%). This sequence change replaces asparagine with histidine at codon 1164 of the KIF1B protein (p.Asn1164His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. |
| Ambry Genetics | RCV002451175 | SCV002612837 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |