ClinVar Miner

Submissions for variant NM_001379500.1(COL18A1):c.107-12197G>A

gnomAD frequency: 0.00063  dbSNP: rs200284308
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000517619 SCV000612884 uncertain significance not specified 2017-01-25 criteria provided, single submitter clinical testing
GeneDx RCV000766954 SCV000619522 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing The R172H variant in the COL18A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is only present in a single alternate transcript of the COL18A1 gene (NM_030582.3), but not in any other known transcript, including the primary isoform used by the Human Gene Mutation database (NM_130445.3). Although not present in the homozygous state, the R172H variant is observed in 53/63514 (0.083%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The R172H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R172H as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000764262 SCV000895275 uncertain significance Knobloch syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000766954 SCV001567957 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing The COL18A1 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_030582.4, and corresponds to NM_130445.2:c.107-12197G>A in the primary transcript. This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 172 of the COL18A1 protein (p.Arg172His). This variant is present in population databases (rs200284308, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with COL18A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 447131). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Ambry Genetics RCV002527466 SCV003713151 uncertain significance Inborn genetic diseases 2021-08-10 criteria provided, single submitter clinical testing The c.515G>A (p.R172H) alteration is located in exon 1 (coding exon 1) of the COL18A1 gene. This alteration results from a G to A substitution at nucleotide position 515, causing the arginine (R) at amino acid position 172 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004553126 SCV004722672 uncertain significance COL18A1-related disorder 2024-02-12 criteria provided, single submitter clinical testing The COL18A1 c.515G>A variant is predicted to result in the amino acid substitution p.Arg172His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.090% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which is likely too frequent for an unreported disease-causing variant. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen RCV000766954 SCV004810471 likely benign not provided 2024-03-01 criteria provided, single submitter clinical testing COL18A1: BP4
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000766954 SCV001800148 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000766954 SCV001969780 likely benign not provided 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.