ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.5681T>C (p.Ile1894Thr)

gnomAD frequency: 0.00001  dbSNP: rs1308170151
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001046651 SCV001210563 uncertain significance Fanconi anemia 2023-04-29 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 843930). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1894 of the FANCM protein (p.Ile1894Thr).
Genetic Services Laboratory, University of Chicago RCV001819760 SCV002064824 uncertain significance not specified 2020-10-06 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCM gene demonstrated a sequence change, c.5681T>C, in exon 21 that results in an amino acid change, p.Ile1894Thr. This sequence change does not appear to have been previously described in patients with FANCM-related disorders and has been described in the gnomAD database in two individuals with an overall population frequency of 0.0008% (dbSNP rs1308170151). The p.Ile1894Thr change affects a moderately conserved amino acid residue located in a domain of the FANCM protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ile1894Thr substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ile1894Thr change remains unknown at this time.
GeneDx RCV004768812 SCV005377912 uncertain significance not provided 2023-10-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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.