Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002008817 | SCV002273266 | uncertain significance | Asphyxiating thoracic dystrophy 5; Senior-Loken syndrome 8 | 2021-05-26 | 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: "Benign"; Align-GVGD: "Class C0". The isoleucine 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 WDR19-related conditions. This variant is present in population databases (rs374891297, ExAC 0.01%). This sequence change replaces methionine with isoleucine at codon 96 of the WDR19 protein (p.Met96Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |
ARUP Laboratories, |
RCV003120795 | SCV003800143 | uncertain significance | not provided | 2022-04-05 | criteria provided, single submitter | clinical testing | The WDR19 c.288G>A; p.Met96Ile variant (rs374891297), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1487764). This variant is found in the African population with an allele frequency of 0.014% (2/14,780 alleles) in the Genome Aggregation Database. The methionine at codon 96 is moderately conserved, but computational analyses predict that this variant is neutral (REVEL: 0.14). Due to limited information, the clinical significance of the p.Met96Ile variant is uncertain at this time. |