NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln) AND LZTR1-related disorder

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 12, 2024
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:: RCV004535698.3

Allele description [Variation Report for NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln)]

NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln)

Other names:

NM_006767.4(LZTR1):c.848G>A

HGVS:

NC_000022.11:g.20991684G>A
NG_034193.1:g.14416G>A
NM_006767.4:c.848G>AMANE SELECT
NP_006758.2:p.Arg283Gln
LRG_989t1:c.848G>A
LRG_989:g.14416G>A
LRG_989p1:p.Arg283Gln
NC_000022.10:g.21345973G>A
NM_006767.3:c.848G>A

Protein change:

R283Q

Links:

dbSNP: rs1223430276

Molecular consequence:

NM_006767.4:c.848G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: LZTR1-related disorder
Synonyms:: LZTR1-related disorders; LZTR1-related condition
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004106725	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Likely pathogenic (Nov 21, 2023)	germline	clinical testing
SCV005873953	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 12, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004106725

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Likely pathogenic
(Nov 21, 2023)

germline

clinical testing

SCV005873953

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 12, 2024)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004106725.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The LZTR1 c.848G>A variant is predicted to result in the amino acid substitution p.Arg283Gln. This variant was reported de novo in two individuals with Noonan syndrome (Umeki et al. 2019. PubMed ID: 30368668; supplementary material, Quaio et al. 2020. PubMed ID: 33258288). This variant was also reported as maternally-inherited in an individual with Noonan syndrome (eTable 2, Maron et al. 2021. PubMed ID: 33587123). In vitro functional studies showed that this variant does not induce the activation of ERK- or ELK-mediated transactivation (Figure S2, Umeki et al. 2019. PubMed ID: 30368668). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic.

#	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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV005873953.1

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

Description

PS4, PM2, PM6_Strong, PP3

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

Last Updated: Jun 27, 2026

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