NM_020533.3(MCOLN1):c.230del (p.Thr77fs) AND Mucolipidosis type IV

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 28, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002035280.4

Allele description [Variation Report for NM_020533.3(MCOLN1):c.230del (p.Thr77fs)]

NM_020533.3(MCOLN1):c.230del (p.Thr77fs)

Gene:

MCOLN1:mucolipin TRP cation channel 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_020533.3(MCOLN1):c.230del (p.Thr77fs)

HGVS:

NC_000019.10:g.7525159del
NG_015806.1:g.7550del
NM_020533.3:c.230delMANE SELECT
NP_065394.1:p.Thr77fs
NC_000019.9:g.7590045del

Protein change:

T77fs

Links:

dbSNP: rs2146021402

NCBI 1000 Genomes Browser:

rs2146021402

Molecular consequence:

NM_020533.3:c.230del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Mucolipidosis type IV (ML4)
Synonyms:: ML IV; Mucolipidosis type 4; ML 4
Identifiers:: MONDO: MONDO:0009653; MedGen: C0238286; Orphanet: 578; OMIM: 252650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236890	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 28, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11030752, 11317355, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236890

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 28, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel.

Sun M, Goldin E, Stahl S, Falardeau JL, Kennedy JC, Acierno JS Jr, Bove C, Kaneski CR, Nagle J, Bromley MC, Colman M, Schiffmann R, Slaugenhaupt SA.

Hum Mol Genet. 2000 Oct 12;9(17):2471-8.

PubMed [citation]

PMID:: 11030752

Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish patients and the frequency of the disease in the Ashkenazi Jewish population.

Bargal R, Avidan N, Olender T, Ben Asher E, Zeigler M, Raas-Rothschild A, Frumkin A, Ben-Yoseph O, Friedlender Y, Lancet D, Bach G.

Hum Mutat. 2001 May;17(5):397-402.

PubMed [citation]

PMID:: 11317355

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236890.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Thr77Argfs*15) 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). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with MCOLN1-related conditions. This variant is not present in population databases (ExAC no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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