NM_006767.4(LZTR1):c.27del (p.Gln10fs) AND Noonan syndrome 2

Germline classification:: Pathogenic (2 submissions)
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:: RCV003388573.3

Allele description [Variation Report for NM_006767.4(LZTR1):c.27del (p.Gln10fs)]

NM_006767.4(LZTR1):c.27del (p.Gln10fs)

Genes:

LOC130067016:ATAC-STARR-seq lymphoblastoid silent region 13504 [Gene]
LZTR1:leucine zipper like post translational regulator 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006767.4(LZTR1):c.27del (p.Gln10fs)

HGVS:

NC_000022.11:g.20982398del
NG_034193.1:g.5130del
NM_006767.4:c.27delMANE SELECT
NP_006758.2:p.Gln10fs
LRG_989t1:c.27del
LRG_989:g.5130del
LRG_989p1:p.Gln10fs
NC_000022.10:g.21336681del
NC_000022.10:g.21336687del
NM_006767.3:c.27del
NM_006767.3:c.27delG
NM_006767.4:c.27delGMANE SELECT

Protein change:

Q10fs

Links:

OMIM: 600574.0004; dbSNP: rs587777613

Molecular consequence:

NM_006767.4:c.27del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Noonan syndrome 2 (NS2)
Identifiers:: MONDO: MONDO:0011531; MedGen: C1854469; Orphanet: 648; OMIM: 605275

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004100499	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV006308720	Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine	no assertion criteria provided	Pathogenic (May 1, 2025)	inherited	clinical testing	PubMed (7) [See all records that cite these PMIDs] 29469822, 30442766, 30859559, 30481304, 30442762, 25335493, 25480913

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004100499

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

SCV006308720

Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine

no assertion criteria provided

Pathogenic
(May 1, 2025)

inherited

clinical testing

PubMed (7)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	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

Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants.

Johnston JJ, van der Smagt JJ, Rosenfeld JA, Pagnamenta AT, Alswaid A, Baker EH, Blair E, Borck G, Brinkmann J, Craigen W, Dung VC, Emrick L, Everman DB, van Gassen KL, Gulsuner S, Harr MH, Jain M, Kuechler A, Leppig KA, McDonald-McGinn DM, Can NTB, Peleg A, et al.

Genet Med. 2018 Oct;20(10):1175-1185. doi: 10.1038/gim.2017.249. Epub 2018 Feb 22.

PubMed [citation]

PMID:: 29469822
PMCID:: PMC6105555

See all PubMed Citations (8)

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV004100499.1

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

Description

The frameshift deletion p.Q10Rfs*15 in LZTR1 (NM_006767.4) has been reported previously in association with schwannomatosis as well as with autosomal recessive Noonan syndrome (Piotrowski et al., 2014; Johnston et al., 2018 et al). This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been proven to be disease causing.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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Reproductive Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, SCV006308720.1

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

Description

Loss-of-function in LZTR1 was an established disease mechanism.This variant caused in a frameshift and a premature stop codon at amino acid position 15 (p.Gln10ArgfsTer15). This variant has been classified as pathogenic in ClinVar (Variation ID: 143931) and has been reported in individuals with Noonan syndrome.

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

Last Updated: Jun 20, 2026

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