NM_020533.3(MCOLN1):c.706C>T (p.Arg236Trp) AND Mucolipidosis type IV

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2022
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:: RCV001982164.5

Allele description [Variation Report for NM_020533.3(MCOLN1):c.706C>T (p.Arg236Trp)]

NM_020533.3(MCOLN1):c.706C>T (p.Arg236Trp)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_020533.3(MCOLN1):c.706C>T (p.Arg236Trp)

HGVS:

NC_000019.10:g.7527889C>T
NG_015806.1:g.10280C>T
NM_020533.3:c.706C>TMANE SELECT
NP_065394.1:p.Arg236Trp
NC_000019.9:g.7592775C>T

Protein change:

R236W

Links:

dbSNP: rs371667920

NCBI 1000 Genomes Browser:

rs371667920

Molecular consequence:

NM_020533.3:c.706C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Hyles Mitogenomics
Hyles Mitogenomics
Mitochondrial genomes as barcodes

BioProject
HIV infection is associated with compromised tumor microenvironment adaptive imm...
HIV infection is associated with compromised tumor microenvironment adaptive immune reactivity in Hodgkin Lymphoma
cHL microenvironment in HIV infection

BioProject
An mRNA processing pathway suppresses metastasis by governing translational cont...
An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus [Ribo-seq, RNA-seq]
An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus [Ribo-seq, RNA-seq]

BioProject

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
SCV002209798	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002209798

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002209798.2

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

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 236 of the MCOLN1 protein (p.Arg236Trp). This variant is present in population databases (rs371667920, gnomAD 0.02%). 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: 1433051). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MCOLN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

ClinVar

Relating variation to medicine