Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001941231 | SCV002208256 | uncertain significance | Fanconi anemia | 2021-07-06 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with threonine at codon 2004 of the FANCM protein (p.Ser2004Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant has not been reported in the literature in individuals affected with FANCM-related conditions. 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. |
| Fulgent Genetics, |
RCV002507619 | SCV002815946 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2021-07-07 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003329423 | SCV004036833 | uncertain significance | not provided | 2023-09-19 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003375468 | SCV004085840 | likely benign | Inborn genetic diseases | 2023-07-26 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |