Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001947730 | SCV002190775 | uncertain significance | Fanconi anemia | 2021-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with isoleucine at codon 787 of the FANCM protein (p.Met787Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (rs201921949, ExAC 0.01%). |
| Ambry Genetics | RCV002556416 | SCV003628355 | uncertain significance | Inborn genetic diseases | 2022-06-09 | criteria provided, single submitter | clinical testing | The c.2361G>A (p.M787I) alteration is located in exon 14 (coding exon 14) of the FANCM gene. This alteration results from a G to A substitution at nucleotide position 2361, causing the methionine (M) at amino acid position 787 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |