ClinVar Miner

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

gnomAD frequency: 0.00003  dbSNP: rs121908373
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Total submissions: 9
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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 2024-07-22 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 21763169, 11317355, 12125810, 34426522, 31589614, 32604955, 31899079, 32426895, 35159355, 11030752)
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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000005443 SCV001395086 pathogenic Mucolipidosis type IV 2024-02-22 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, 37972748). This variant is present in population databases (rs121908373, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with mucolipidosis type IV (PMID: 11030752). ClinVar contains an entry for this variant (Variation ID: 5136). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000005443 SCV002809126 pathogenic Mucolipidosis type IV 2021-10-15 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000005443 SCV005073860 pathogenic Mucolipidosis type IV criteria provided, single submitter clinical testing The observed stop gained variant c.304C>T (p.Arg102Ter) in MCOLN1 gene has been reported in homozygous and compound heterozygous state in multiple individuals affected with Mucolipidosis IV (ezela-Stanek A et al. 2020; Zhang S et al. 2017; Wakabayashi K et al. 2011). The p.Arg102Ter variant has allele frequency 0.002% in gnomAD Exomes. This variant has been submitted to the ClinVar database as Likely Pathogenic / Pathogenic (multiple submitters). The nucleotide change c.304C>T in MCOLN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in MCOLN1 are known to be pathogenic (Sun M et al. 2000). For these reasons, this variant has been classified as Pathogenic.
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

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