Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000693498 | SCV000821369 | uncertain significance | Fanconi anemia | 2023-09-11 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1653 of the FANCM protein (p.Met1653Ile). This variant is present in population databases (rs143152888, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 572179). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Gene |
RCV001562968 | SCV001785824 | uncertain significance | not provided | 2022-10-20 | criteria provided, single submitter | clinical testing | 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 |
| Fulgent Genetics, |
RCV002493185 | SCV002800797 | uncertain significance | Spermatogenic failure 28; Premature ovarian failure 15 | 2022-05-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004619388 | SCV005113463 | uncertain significance | Inborn genetic diseases | 2024-05-14 | criteria provided, single submitter | clinical testing | The c.4959G>A (p.M1653I) alteration is located in exon 20 (coding exon 20) of the FANCM gene. This alteration results from a G to A substitution at nucleotide position 4959, causing the methionine (M) at amino acid position 1653 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Mendelics | RCV004702332 | SCV005205572 | likely benign | Hereditary cancer | 2024-09-11 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following: it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease, and/or has normal protein function, and/or has lack of segregation with disease, and/or has been detected in co-occurrence with known pathogenic variant, and/or has lack of disease association in case-control studies, and/or is located in a region inconsistent with a known cause of pathogenicity. |