NM_015166.4(MLC1):c.240G>A (p.Met80Ile) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 25, 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:: RCV000059742.2

Allele description [Variation Report for NM_015166.4(MLC1):c.240G>A (p.Met80Ile)]

NM_015166.4(MLC1):c.240G>A (p.Met80Ile)

Genes:

LOC125446261:Sharpr-MPRA regulatory region 9327 [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.240G>A (p.Met80Ile)

HGVS:

NC_000022.11:g.50083111C>T
NG_009162.1:g.7819G>A
NM_001376472.1:c.240G>A
NM_001376473.1:c.240G>A
NM_001376474.1:c.240G>A
NM_001376475.1:c.240G>A
NM_001376476.1:c.240G>A
NM_001376477.1:c.240G>A
NM_001376478.1:c.240G>A
NM_001376479.1:c.240G>A
NM_001376480.1:c.177+1615G>A
NM_001376481.1:c.240G>A
NM_001376482.1:c.240G>A
NM_001376483.1:c.240G>A
NM_001376484.1:c.3G>A
NM_015166.4:c.240G>AMANE SELECT
NM_139202.3:c.240G>A
NP_001363401.1:p.Met80Ile
NP_001363402.1:p.Met80Ile
NP_001363403.1:p.Met80Ile
NP_001363404.1:p.Met80Ile
NP_001363405.1:p.Met80Ile
NP_001363406.1:p.Met80Ile
NP_001363407.1:p.Met80Ile
NP_001363408.1:p.Met80Ile
NP_001363410.1:p.Met80Ile
NP_001363411.1:p.Met80Ile
NP_001363412.1:p.Met80Ile
NP_001363413.1:p.Met1Ile
NP_055981.1:p.Met80Ile
NP_055981.1:p.Met80Ile
NP_631941.1:p.Met80Ile
NC_000022.10:g.50521540C>T
NM_015166.3:c.240G>A
NR_164811.1:n.587G>A
NR_164812.1:n.371G>A
NR_164813.1:n.764G>A
Q15049:p.Met80Ile

Protein change:

M1I

Links:

UniProtKB: Q15049#VAR_067763; UniProtKB/Swiss-Prot: VAR_067763; dbSNP: rs281875310

NCBI 1000 Genomes Browser:

rs281875310

Molecular consequence:

NM_001376484.1:c.3G>A - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001376480.1:c.177+1615G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001376472.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376473.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376474.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376475.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376476.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376477.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376478.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376479.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376481.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376482.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376483.1:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001376484.1:c.3G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_015166.4:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139202.3:c.240G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_164811.1:n.587G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164812.1:n.371G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164813.1:n.764G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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
SCV000091312	UniProtKB/Swiss-Prot	no classification provided	not provided	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV003444349	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16652334, 16470554, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000091312

UniProtKB/Swiss-Prot

no classification provided

not provided

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

SCV003444349

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 25, 2022)

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Megalencephalic leukoencephalopathy with subcortical cysts: an update and extended mutation analysis of MLC1.

Ilja Boor PK, de Groot K, Mejaski-Bosnjak V, Brenner C, van der Knaap MS, Scheper GC, Pronk JC.

Hum Mutat. 2006 Jun;27(6):505-12.

PubMed [citation]

PMID:: 16652334

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

See all PubMed Citations (3)

Details of each submission

From UniProtKB/Swiss-Prot, SCV000091312.2

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

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

From Invitae, SCV003444349.2

#	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 replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 80 of the MLC1 protein (p.Met80Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of megalencephalic leukoencephalopathy with subcortical cysts (PMID: 16652334; Invitae). ClinVar contains an entry for this variant (Variation ID: 68790). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Met80 amino acid residue in MLC1. Other variant(s) that disrupt this residue have been observed in individuals with MLC1-related conditions (PMID: 16470554), which suggests that this may be a clinically significant amino acid residue. 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: Feb 4, 2024

ClinVar

Relating variation to medicine