NM_015166.4(MLC1):c.274C>T (p.Pro92Ser) AND Megalencephalic leukoencephalopathy with subcortical cysts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 24, 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:: RCV001844006.1

Allele description [Variation Report for NM_015166.4(MLC1):c.274C>T (p.Pro92Ser)]

NM_015166.4(MLC1):c.274C>T (p.Pro92Ser)

Gene:

MLC1:modulator of VRAC current 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_015166.4(MLC1):c.274C>T (p.Pro92Ser)

HGVS:

NC_000022.11:g.50080391G>A
NG_009162.1:g.10539C>T
NM_001376472.1:c.274C>T
NM_001376473.1:c.274C>T
NM_001376474.1:c.274C>T
NM_001376475.1:c.274C>T
NM_001376476.1:c.274C>T
NM_001376477.1:c.274C>T
NM_001376478.1:c.274C>T
NM_001376479.1:c.274C>T
NM_001376480.1:c.184C>T
NM_001376481.1:c.274C>T
NM_001376482.1:c.267+2693C>T
NM_001376483.1:c.267+2693C>T
NM_001376484.1:c.37C>T
NM_015166.4:c.274C>TMANE SELECT
NM_139202.3:c.274C>T
NP_001363401.1:p.Pro92Ser
NP_001363402.1:p.Pro92Ser
NP_001363403.1:p.Pro92Ser
NP_001363404.1:p.Pro92Ser
NP_001363405.1:p.Pro92Ser
NP_001363406.1:p.Pro92Ser
NP_001363407.1:p.Pro92Ser
NP_001363408.1:p.Pro92Ser
NP_001363409.1:p.Pro62Ser
NP_001363410.1:p.Pro92Ser
NP_001363413.1:p.Pro13Ser
NP_055981.1:p.Pro92Ser
NP_055981.1:p.Pro92Ser
NP_631941.1:p.Pro92Ser
NC_000022.10:g.50518820G>A
NM_001376474.1:c.274C>T
NM_015166.3:c.274C>T
NR_164811.1:n.621C>T
NR_164812.1:n.405C>T
NR_164813.1:n.798C>T
Q15049:p.Pro92Ser

Protein change:

P13S; PRO92SER

Links:

UniProtKB: Q15049#VAR_017439; OMIM: 605908.0007; dbSNP: rs121908345

NCBI 1000 Genomes Browser:

rs121908345

Molecular consequence:

NM_001376482.1:c.267+2693C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001376483.1:c.267+2693C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001376472.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376473.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376474.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376475.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376476.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376477.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376478.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376479.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376480.1:c.184C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376481.1:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001376484.1:c.37C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_015166.4:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139202.3:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_164811.1:n.621C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164812.1:n.405C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164813.1:n.798C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Megalencephalic leukoencephalopathy with subcortical cysts
Synonyms:: VAN DER KNAAP DISEASE
Identifiers:: MONDO: MONDO:0011391; MedGen: C1858854

Recent activity

Clear Turn Off Turn On

RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 1; AltName...
RecName: Full=Carcinoembryonic antigen-related cell adhesion molecule 1; AltName: Full=Biliary glycoprotein 1; Short=BGP-1; AltName: Full=Biliary glycoprotein D; AltName: Full=MHVR1; AltName: Full=Murine hepatitis virus receptor; Short=MHV-R; AltName: CD_antigen=CD66a; Flags: Precursor
gi|399117|sp|P31809.1|CEAM1_MOUSE

Protein

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
SCV002103896	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 24, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16470554, 12189496, 18757878, 11935341 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002103896

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 24, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Vacuolating megalencephalic leukoencephalopathy with subcortical cysts: functional studies of novel variants in MLC1.

Montagna G, Teijido O, Eymard-Pierre E, Muraki K, Cohen B, Loizzo A, Grosso P, Tedeschi G, Palacín M, Boespflug-Tanguy O, Bertini E, Santorelli FM, Estévez R.

Hum Mutat. 2006 Mar;27(3):292.

PubMed [citation]

PMID:: 16470554

Megalencephalic leukoencephalopathy with subcortical cysts; a founder effect in Israeli patients and a higher than expected carrier rate among Libyan Jews.

Ben-Zeev B, Levy-Nissenbaum E, Lahat H, Anikster Y, Shinar Y, Brand N, Gross-Tzur V, MacGregor D, Sidi R, Kleta R, Frydman M, Pras E.

Hum Genet. 2002 Aug;111(2):214-8. Epub 2002 Jul 16.

PubMed [citation]

PMID:: 12189496

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103896.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: MLC1 c.274C>T (p.Pro92Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00013 in 232710 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MLC1 causing Megalencephalic Leukoencephalopathy With Subcortical Cysts 1 (0.00013 vs 0.0011), allowing no conclusion about variant significance. c.274C>T has been reported in the literature in multiple individuals affected with Megalencephalic Leukoencephalopathy With Subcortical Cysts 1 (example, Leegwater_2002, Ben-Zeev_2002, Montagna_2006). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (example Duarri_2008). The most pronounced variant effect results in localization within the lysosomes after internalization from the plasma membrane. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was 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: Oct 8, 2024

ClinVar

Relating variation to medicine