NM_015166.3(MLC1):c.274C>T (p.Pro92Ser) AND Megalencephalic leukoencephalopathy with subcortical cysts 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jan 8, 2016
Review status:: criteria provided, conflicting classifications

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:: RCV000004984.3

Allele description

NM_015166.3(MLC1):c.274C>T (p.Pro92Ser)

Gene:

MLC1:megalencephalic leukoencephalopathy with subcortical cysts 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_015166.3(MLC1):c.274C>T (p.Pro92Ser)

HGVS:

NC_000022.11:g.50080391G>A
NG_009162.1:g.10539C>T
NM_015166.3:c.274C>T
NP_055981.1:p.Pro92Ser
NC_000022.10:g.50518820G>A
Q15049:p.Pro92Ser

Protein change:

P92S; PRO92SER

Links:

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

NCBI 1000 Genomes Browser:

rs121908345

Allele Frequency:

0.00021(A)

Molecular consequence:

NM_015166.3:c.274C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1)
Synonyms:: VAN DER KNAAP DISEASE; Megalencephalic leukoencephalopathy with subcortical cysts
Identifiers:: MedGen: C1858854; Orphanet: 2478; OMIM: 604004

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
SCV000025160	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 2002)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 11935341, 11254442, 12189496
SCV000485560	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Jan 8, 2016)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 18757878, 11935341, 12189496, 21145992, 16470554, 23793458, 22405205 mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025160

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 2002)

germline

literature only

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

SCV000485560

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Jan 8, 2016)

unknown

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts.

Leegwater PA, Yuan BQ, van der Steen J, Mulders J, Könst AA, Boor PK, Mejaski-Bosnjak V, van der Maarel SM, Frants RR, Oudejans CB, Schutgens RB, Pronk JC, van der Knaap MS.

Am J Hum Genet. 2001 Apr;68(4):831-8. Epub 2001 Mar 6.

PubMed [citation]

PMID:: 11254442
PMCID:: PMC1275636

Molecular pathogenesis of megalencephalic leukoencephalopathy with subcortical cysts: mutations in MLC1 cause folding defects.

Duarri A, Teijido O, López-Hernández T, Scheper GC, Barriere H, Boor I, Aguado F, Zorzano A, Palacín M, Martínez A, Lukacs GL, van der Knaap MS, Nunes V, Estévez R.

Hum Mol Genet. 2008 Dec 1;17(23):3728-39. doi: 10.1093/hmg/ddn269. Epub 2008 Aug 30.

PubMed [citation]

PMID:: 18757878
PMCID:: PMC2581428

See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000025160.2

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

Description

In 3 unrelated families with megalencephalic leukoencephalopathy with subcortical cysts (MLC1; 604004), 2 from Croatia and 1 from U.K./Eastern Europe, Leegwater et al. (2002) found compound heterozygosity for mutations in the MLC1 gene, with 1 of the alleles carrying a pro92-to-ser (P92S) missense mutation. The amino acid change resulted from a C-to-T transition at nucleotide 274. In the U.K./Eastern Europe case, the second mutation was tyr198-to-ter (605908.0008), described by Leegwater et al. (2001).

In a family of mixed Jewish ancestry (the father a Libyan Jew and the mother an Ashkenazi Jew) with megalencephalic leukoencephalopathy with subcortical cysts, Ben-Zeev et al. (2002) identified the P92S substitution. The mutation was not found in 140 unaffected Ashkenazi control chromosomes.

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

From Counsyl, SCV000485560.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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

Last Updated: Jan 6, 2018

ClinVar

Relating variation to medicine