ClinVar Miner

Submissions for variant NM_017777.4(MKS1):c.1613G>A (p.Arg538His)

gnomAD frequency: 0.00002  dbSNP: rs557678962
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001205145 SCV001376385 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 538 of the MKS1 protein (p.Arg538His). This variant is present in population databases (rs557678962, gnomAD 0.05%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 936361). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
GeneDx RCV001546224 SCV001765707 uncertain significance not provided 2020-03-09 criteria provided, single submitter clinical testing 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
New York Genome Center RCV003227934 SCV003925138 uncertain significance Bardet-Biedl syndrome 13; Meckel syndrome, type 1; Joubert syndrome 28 2022-05-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV003346361 SCV004066343 uncertain significance Inborn genetic diseases 2023-08-14 criteria provided, single submitter clinical testing The c.1613G>A (p.R538H) alteration is located in exon 18 (coding exon 18) of the MKS1 gene. This alteration results from a G to A substitution at nucleotide position 1613, causing the arginine (R) at amino acid position 538 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001833802 SCV002087604 uncertain significance Meckel syndrome, type 1 2020-01-03 no assertion criteria provided clinical testing

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.