ClinVar Miner

Submissions for variant NM_032444.4(SLX4):c.3648G>T (p.Gln1216His) (rs139544666)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231468 SCV000291079 uncertain significance Fanconi anemia 2019-02-19 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1216 of the SLX4 protein (p.Gln1216His). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs139544666, ExAC 0.02%) but has not been reported in the literature in individuals with a SLX4-related disease. ClinVar contains an entry for this variant (Variation ID: 241680). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Genetic Services Laboratory, University of Chicago RCV000502983 SCV000597159 uncertain significance not specified 2017-02-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001121726 SCV001280372 uncertain significance Fanconi anemia, complementation group P 2018-01-12 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.