Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001318082 | SCV001508770 | uncertain significance | not provided | 2022-01-07 | 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1018742). This variant has not been reported in the literature in individuals affected with WHRN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 126 of the WHRN protein (p.Ala126Thr). |
| Laboratory for Molecular Medicine, |
RCV001449730 | SCV001652996 | likely benign | not specified | 2020-09-28 | criteria provided, single submitter | clinical testing | The p.Ala126Thr variant in WHRN is classified as likely benign due to a lack of conservation across species. Four mammals (dolphin, killer whale, Cape elephant shrew, Cape golden mole) carry a threonine (Thr) at this position despite high nearby amino acid conservation. ACMG/AMP Criteria applied: BP4_Strong. |