Total submissions: 5
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, |
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, |
RCV000194725 | SCV002812699 | pathogenic | Mucolipidosis type IV | 2022-02-15 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000194725 | SCV002091385 | pathogenic | Mucolipidosis type IV | 2017-11-29 | no assertion criteria provided | clinical testing |