Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051827 | SCV001216005 | uncertain significance | Fanconi anemia | 2019-05-20 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals 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 alanine 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 is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 1957 of the FANCM protein (p.Val1957Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. |
Gene |
RCV001585950 | SCV001820459 | uncertain significance | not provided | 2020-09-11 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); 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 |