Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000541605 | SCV000626314 | uncertain significance | Fanconi anemia | 2017-06-14 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with tyrosine at codon 1278 of the FANCI protein (p.His1278Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs776134519, ExAC 0.03%). This variant has not been reported in the literature in individuals with a FANCI-related disease. 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 tyrosine 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. In summary, this variant has uncertain impact on FANCI function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Illumina Laboratory Services, |
RCV001117648 | SCV001275857 | uncertain significance | Fanconi anemia, complementation group I | 2018-03-23 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |