NM_014975.3(MAST1):c.865C>G (p.Leu289Val) AND Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 2, 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:: RCV002471610.1

Allele description [Variation Report for NM_014975.3(MAST1):c.865C>G (p.Leu289Val)]

NM_014975.3(MAST1):c.865C>G (p.Leu289Val)

Gene:

MAST1:microtubule associated serine/threonine kinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.13

Genomic location:

Preferred name:

NM_014975.3(MAST1):c.865C>G (p.Leu289Val)

HGVS:

NC_000019.10:g.12852024C>G
NG_054729.1:g.23094C>G
NM_014975.3:c.865C>GMANE SELECT
NP_055790.1:p.Leu289Val
NC_000019.9:g.12962838C>G
NM_014975.2:c.865C>G

Protein change:

L289V

Molecular consequence:

NM_014975.3:c.865C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations
Identifiers:: MONDO: MONDO:0032648; MedGen: C4748927; OMIM: 618273

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002769013	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 2, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30449657, 32198973, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002769013

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 2, 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

Citations

PubMed

Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations.

Tripathy R, Leca I, van Dijk T, Weiss J, van Bon BW, Sergaki MC, Gstrein T, Breuss M, Tian G, Bahi-Buisson N, Paciorkowski AR, Pagnamenta AT, Wenninger-Weinzierl A, Martinez-Reza MF, Landler L, Lise S, Taylor JC, Terrone G, Vitiello G, Del Giudice E, Brunetti-Pierri N, D'Amico A, et al.

Neuron. 2018 Dec 19;100(6):1354-1368.e5. doi: 10.1016/j.neuron.2018.10.044. Epub 2018 Nov 15.

PubMed [citation]

PMID:: 30449657
PMCID:: PMC6436622

MAST1 variant causes mega-corpus-callosum syndrome with cortical malformations but without cerebellar hypoplasia.

Rodríguez-García ME, Cotrina-Vinagre FJ, Gómez-Cano MLÁ, Martínez de Aragón A, Martín-Hernández E, Martínez-Azorín F.

Am J Med Genet A. 2020 Jun;182(6):1483-1490. doi: 10.1002/ajmg.a.61560. Epub 2020 Mar 21.

PubMed [citation]

PMID:: 32198973

See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002769013.1

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. However, gain of function and dominant negative have been reported (PMIDs: 30449657, 32198973). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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: Dec 24, 2022

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