NM_006767.4(LZTR1):c.848G>A (p.Arg283Gln) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Dec 20, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000681082.27

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000808536	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 15, 2021)	germline	clinical testing	Citation Link,
SCV001917340	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001956355	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002817313	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	pathogenic (Aug 22, 2024)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 30368668, 30859559, 33258288, 33587123, 35253369, 35979676, 26467025
SCV003254428	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 20, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 33258288, 30368668, 28492532
SCV003832268	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 18, 2022)	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Delineation of dominant and recessive forms of LZTR1-associated Noonan syndrome.

Pagnamenta AT, Kaisaki PJ, Bennett F, Burkitt-Wright E, Martin HC, Ferla MP, Taylor JM, Gompertz L, Lahiri N, Tatton-Brown K, Newbury-Ecob R, Henderson A, Joss S, Weber A, Carmichael J, Turnpenny PD, McKee S, Forzano F, Ashraf T, Bradbury K, Shears D, Kini U, et al.

Clin Genet. 2019 Jun;95(6):693-703. doi: 10.1111/cge.13533. Epub 2019 Apr 3.

PubMed [citation]

PMID:: 30859559
PMCID:: PMC6563422

Novel Variant Findings and Challenges Associated With the Clinical Integration of Genomic Testing: An Interim Report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study.

Maron JL, Kingsmore SF, Wigby K, Chowdhury S, Dimmock D, Poindexter B, Suhrie K, Vockley J, Diacovo T, Gelb BD, Stroustrup A, Powell CM, Trembath A, Gallen M, Mullen TE, Tanpaiboon P, Reed D, Kurfiss A, Davis JM.

JAMA Pediatr. 2021 May 1;175(5):e205906. doi: 10.1001/jamapediatrics.2020.5906. Epub 2021 May 3. Erratum in: JAMA Pediatr. 2021 Aug 1;175(8):871. doi: 10.1001/jamapediatrics.2021.1977..

PubMed [citation]

PMID:: 33587123
PMCID:: PMC7885094

See all PubMed Citations (9)

Details of each submission

From GeneDx, SCV000808536.4

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

Description

Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 30368668, 33258288, 33792302)

#	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

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001917340.1

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

#	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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001956355.1

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

#	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

From Athena Diagnostics, SCV002817313.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. This variant segregates with disease in multiple families. This variant appears to occur de novo in one individual with clinical features associated with this gene.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003254428.4

#	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 283 of the LZTR1 protein (p.Arg283Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Noonan syndrome (PMID: 30368668, 33258288; internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 561716). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt LZTR1 protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on LZTR1 function (PMID: 30368668). For these reasons, this variant has been classified as 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 Revvity Omics, Revvity, SCV003832268.3

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

#	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: Jun 27, 2026

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