NM_006767.4(LZTR1):c.742G>A (p.Gly248Arg) AND Noonan syndrome 10

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 1, 2015
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000191027.2

Allele description

NM_006767.4(LZTR1):c.742G>A (p.Gly248Arg)

Gene:

LZTR1:leucine zipper like transcription regulator 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006767.4(LZTR1):c.742G>A (p.Gly248Arg)

HGVS:

NC_000022.11:g.20990476G>A
NG_034193.1:g.13208G>A
NM_006767.4:c.742G>A
NP_006758.2:p.Gly248Arg
NC_000022.10:g.21344765G>A
NM_006767.3:c.742G>A
Q8N653:p.Gly248Arg

Protein change:

G248R; GLY248ARG

Links:

UniProtKB: Q8N653#VAR_075659; OMIM: 600574.0008; dbSNP: rs869320686

NCBI 1000 Genomes Browser:

rs869320686

Molecular consequence:

NM_006767.4:c.742G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome 10 (NS10)
Identifiers:: MedGen: C4225280; Orphanet: 648; OMIM: 616564

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000246007	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2015)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 25795793, 30442762

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000246007

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2015)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome.

Yamamoto GL, Aguena M, Gos M, Hung C, Pilch J, Fahiminiya S, Abramowicz A, Cristian I, Buscarilli M, Naslavsky MS, Malaquias AC, Zatz M, Bodamer O, Majewski J, Jorge AA, Pereira AC, Kim CA, Passos-Bueno MR, Bertola DR.

J Med Genet. 2015 Jun;52(6):413-21. doi: 10.1136/jmedgenet-2015-103018. Epub 2015 Mar 20.

PubMed [citation]

PMID:: 25795793

Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.

Steklov M, Pandolfi S, Baietti MF, Batiuk A, Carai P, Najm P, Zhang M, Jang H, Renzi F, Cai Y, Abbasi Asbagh L, Pastor T, De Troyer M, Simicek M, Radaelli E, Brems H, Legius E, Tavernier J, Gevaert K, Impens F, Messiaen L, Nussinov R, et al.

Science. 2018 Dec 7;362(6419):1177-1182. doi: 10.1126/science.aap7607. Epub 2018 Nov 15.

PubMed [citation]

PMID:: 30442762
PMCID:: PMC8058620

Details of each submission

From OMIM, SCV000246007.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In 3 members of a Brazilian family (Br-F3) with Noonan syndrome-10 (NS10; 616564), Yamamoto et al. (2015) identified a heterozygous c.742G-A transition (c.742G-A, NM_006767.3) in exon 8 of the LZTR1 gene, resulting in a gly248-to-arg (G248R) substitution in the KT4 domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was filtered against the 1000 Genomes Project and Exome Sequencing Project databases and 609 Brazilian controls. Functional studies of the variant were not performed.

Steklov et al. (2018) found that LZTR1 Kelch domain mutants, including G248R, showed decreased binding to RAS in coimmunoprecipitation assays.

#	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

Last Updated: Nov 2, 2019

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