NM_015166.4(MLC1):c.973C>T (p.Gln325Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 4, 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:: RCV001861366.4

Allele description [Variation Report for NM_015166.4(MLC1):c.973C>T (p.Gln325Ter)]

NM_015166.4(MLC1):c.973C>T (p.Gln325Ter)

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.973C>T (p.Gln325Ter)

HGVS:

NC_000022.11:g.50064120G>A
NG_009162.1:g.26810C>T
NM_001376472.1:c.973C>T
NM_001376473.1:c.973C>T
NM_001376474.1:c.973C>T
NM_001376475.1:c.973C>T
NM_001376476.1:c.973C>T
NM_001376477.1:c.973C>T
NM_001376478.1:c.973C>T
NM_001376479.1:c.916C>T
NM_001376480.1:c.883C>T
NM_001376481.1:c.871C>T
NM_001376482.1:c.817C>T
NM_001376483.1:c.817C>T
NM_001376484.1:c.736C>T
NM_015166.4:c.973C>TMANE SELECT
NM_139202.3:c.973C>T
NP_001363401.1:p.Gln325Ter
NP_001363402.1:p.Gln325Ter
NP_001363403.1:p.Gln325Ter
NP_001363404.1:p.Gln325Ter
NP_001363405.1:p.Gln325Ter
NP_001363406.1:p.Gln325Ter
NP_001363407.1:p.Gln325Ter
NP_001363408.1:p.Gln306Ter
NP_001363409.1:p.Gln295Ter
NP_001363410.1:p.Gln291Ter
NP_001363411.1:p.Gln273Ter
NP_001363412.1:p.Gln273Ter
NP_001363413.1:p.Gln246Ter
NP_055981.1:p.Gln325Ter
NP_055981.1:p.Gln325Ter
NP_631941.1:p.Gln325Ter
NC_000022.10:g.50502549G>A
NM_015166.3:c.973C>T
NR_164811.1:n.1320C>T
NR_164812.1:n.1104C>T
NR_164813.1:n.1497C>T

Protein change:

Q246*

Links:

dbSNP: rs1057516465

NCBI 1000 Genomes Browser:

rs1057516465

Molecular consequence:

NR_164811.1:n.1320C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164812.1:n.1104C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_164813.1:n.1497C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001376472.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376473.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376474.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376475.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376476.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376477.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376478.1:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376479.1:c.916C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376480.1:c.883C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376481.1:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376482.1:c.817C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376483.1:c.817C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001376484.1:c.736C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015166.4:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_139202.3:c.973C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002151416	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11254442, 16470554, 24824219, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002151416

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 4, 2022)

germline

clinical testing

PubMed (4)
[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

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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002151416.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370408). This variant has not been reported in the literature in individuals affected with MLC1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.008%). This sequence change creates a premature translational stop signal (p.Gln325*) in the MLC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLC1 are known to be pathogenic (PMID: 11254442, 16470554, 24824219).

#	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

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