Submissions for variant NM_020533.3(MCOLN1):c.1453_1463dup (p.Ser488fs)

dbSNP: rs797044823

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000193040	SCV000699452	pathogenic	Mucolipidosis type IV	2016-09-22	criteria provided, single submitter	clinical testing	Variant summary: The MCOLN1 c.1453_1463dup11 (p.Ser488Argfs) variant was classified as pathogenic. It is a frameshift mutation predicted to alter the 580 amino acid long MCOLN1 protein starting at position 488 and resulting in a STOP codon 96 amino acids downstream. The variant likely results in a loss of protein function due to nonsense mediated decay or due to production of an abnormal protein. Mutation taster predicts the variant to be disease causing. The variant is absent from the general population, while it was reported in Mucolipidosis type IV patients indicating pathogenicity. Databases list the variant with a classification of pathogenic. Considering all evidence, the variant was classified as pathogenic.
Baylor Genetics	RCV000193040	SCV001163815	pathogenic	Mucolipidosis type IV		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000193040	SCV003442654	pathogenic	Mucolipidosis type IV	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the MCOLN1 gene (p.Ser488Argfs*96). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 93 amino acid(s) of the MCOLN1 protein and extend the protein by 2 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This frameshift has been observed in individual(s) with MCOLN1-related conditions (PMID: 11317355, 12182165). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 208029). This variant disrupts a region of the MCOLN1 protein in which other variant(s) (p.Ala539Profs*41) have been determined to be pathogenic (PMID: 18326692). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005016547	SCV005648828	likely pathogenic	Mucolipidosis type IV; Lisch epithelial corneal dystrophy	2024-05-23	criteria provided, single submitter	clinical testing
GeneReviews	RCV000193040	SCV000243830	not provided	Mucolipidosis type IV		no assertion provided	literature only
Natera, Inc.	RCV000193040	SCV002091409	pathogenic	Mucolipidosis type IV	2017-11-29	no assertion criteria provided	clinical testing