ClinVar Miner

Submissions for variant NM_020533.3(MCOLN1):c.920del (p.Leu307fs)

gnomAD frequency: 0.00003  dbSNP: rs755042147
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000194725 SCV000485607 likely pathogenic Mucolipidosis type IV 2016-01-12 criteria provided, single submitter clinical testing
Invitae RCV000194725 SCV000938348 pathogenic Mucolipidosis type IV 2023-12-12 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu307Profs*65) 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 (rs755042147, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with mucolipidosis type IV (PMID: 18326692). ClinVar contains an entry for this variant (Variation ID: 208039). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000194725 SCV001427011 pathogenic Mucolipidosis type IV 2020-07-30 criteria provided, single submitter clinical testing Variant summary: MCOLN1 c.920delT (p.Leu307ProfsX65) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251390 control chromosomes (gnomAD). c.920delT has been reported in the literature in one individual affected with Mucolipidosis Type 4 (Goldin_2008). These data indicate that the variant may be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (2x) and likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000194725 SCV002812699 pathogenic Mucolipidosis type IV 2022-02-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV000194725 SCV002091385 pathogenic Mucolipidosis type IV 2017-11-29 no assertion criteria provided clinical testing

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