Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002028861 | SCV002296527 | uncertain significance | Fanconi anemia | 2020-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1912 of the FANCM protein (p.Phe1912Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. 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 leucine 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 FANCM-related conditions. This variant is present in population databases (rs755903696, ExAC 0.002%). |
Ambry Genetics | RCV004976139 | SCV005587004 | uncertain significance | Inborn genetic diseases | 2024-12-04 | criteria provided, single submitter | clinical testing | The p.F1912L variant (also known as c.5736T>A), located in coding exon 22 of the FANCM gene, results from a T to A substitution at nucleotide position 5736. The phenylalanine at codon 1912 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |