ClinVar Miner

Submissions for variant NM_020533.3(MCOLN1):c.304C>T (p.Arg102Ter)

gnomAD frequency: 0.00003  dbSNP: rs121908373
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000498354 SCV000331818 pathogenic not provided 2016-08-17 criteria provided, single submitter clinical testing
GeneDx RCV000498354 SCV000589341 pathogenic not provided 2018-08-23 criteria provided, single submitter clinical testing The R102X pathogenic variant in the MCOLN1 gene has been reported previously in an individual with mucolipidosis type IV who also possessed a second variant in the MCOLN1 gene (Sun et al., 2001). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R102X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R102X as a pathogenic variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000005443 SCV000699454 pathogenic Mucolipidosis type IV 2017-06-23 criteria provided, single submitter clinical testing Variant summary: The MCOLN1 c.304C>T (p.Arg102X) variant results in a premature termination codon, predicted to cause a truncated or absent MCOLN1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position have been classified as pathogenic by our laboratory , c.1615delG (p.Ala539fsX41). This variant was found in 6/121384 control chromosomes at a frequency of 0.0000494, which does not exceed the estimated maximal expected allele frequency of a pathogenic MCOLN1 variant (0.0030619). A publication cites this variant in an affected compound heterozygote individual. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000005443 SCV001395086 pathogenic Mucolipidosis type IV 2023-09-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg102*) in the MCOLN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCOLN1 are known to be pathogenic (PMID: 11030752, 11317355). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 5136). This premature translational stop signal has been observed in individual(s) with mucolipidosis type IV (PMID: 11030752). This variant is present in population databases (rs121908373, gnomAD 0.007%).
Fulgent Genetics, Fulgent Genetics RCV000005443 SCV002809126 pathogenic Mucolipidosis type IV 2021-10-15 criteria provided, single submitter clinical testing
OMIM RCV000005443 SCV000025625 pathogenic Mucolipidosis type IV 2000-10-12 no assertion criteria provided literature only
Counsyl RCV000005443 SCV001132246 likely pathogenic Mucolipidosis type IV 2015-07-22 no assertion criteria provided clinical testing
Natera, Inc. RCV000005443 SCV002091365 pathogenic Mucolipidosis type IV 2017-03-17 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.