NM_020533.3(MCOLN1):c.608del (p.Pro203fs) AND Mucolipidosis type IV

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 25, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002306886.3

Allele description [Variation Report for NM_020533.3(MCOLN1):c.608del (p.Pro203fs)]

NM_020533.3(MCOLN1):c.608del (p.Pro203fs)

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.608del (p.Pro203fs)

HGVS:

NC_000019.10:g.7527556del
NG_015806.1:g.9947del
NM_020533.3:c.608delMANE SELECT
NP_065394.1:p.Pro203fs
NC_000019.9:g.7592441del
NC_000019.9:g.7592442del

Protein change:

P203fs

Molecular consequence:

NM_020533.3:c.608del - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002603978	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Likely pathogenic (Apr 13, 2022)	unknown	clinical testing	Citation Link,
SCV004309431	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 25, 2023)	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

SCV002603978

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Likely pathogenic
(Apr 13, 2022)

unknown

clinical testing

Citation Link,

SCV004309431

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 25, 2023)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Myriad Genetics, Inc., SCV002603978.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

NM_020533.2(MCOLN1):c.608delC(P203Rfs*35) is expected to be pathogenic in the context of mucolipidosis IV. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in MCOLN1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.

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

From Invitae, SCV004309431.1

#	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.Pro203Argfs*35) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MCOLN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1725915). For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 20, 2024

ClinVar

Relating variation to medicine