Submissions for variant NM_020533.3(MCOLN1):c.615dup (p.Ser206fs)

dbSNP: rs886041533

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000368147	SCV000330206	pathogenic	not provided	2016-01-21	criteria provided, single submitter	clinical testing	The c.615dupC pathogenic variant in the MCOLN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.615dupC variant causes a frameshift starting with codon Serine 206, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Ser206GlnfsX36. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.615dupC variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.615dupC as a pathogenic variant.
Invitae	RCV001855065	SCV002225883	pathogenic	Mucolipidosis type IV	2022-01-18	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MCOLN1-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280304). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser206Glnfs*36) 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).