NM_006767.4(LZTR1):c.27del (p.Gln10fs) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jan 26, 2026
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:: RCV000680837.51

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]

Observations:

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
SCV000808286	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 2, 2023)	germline	clinical testing	Citation Link,
SCV001249399	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2019)	germline	clinical testing	Citation Link,
SCV001578236	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 26, 2026)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 25335493, 25795793, 30368668, 30442762, 30442766, 30481304, 30859559, 24362817, 25480913, 29469822, 28492532
SCV006318388	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 29, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007601957	Dasa	no assertion criteria provided	Pathogenic (Sep 17, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24362817, 25480913, 29469822

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
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanding the mutational spectrum of LZTR1 in schwannomatosis.

Paganini I, Chang VY, Capone GL, Vitte J, Benelli M, Barbetti L, Sestini R, Trevisson E, Hulsebos TJ, Giovannini M, Nelson SF, Papi L.

Eur J Hum Genet. 2015 Jul;23(7):963-8. doi: 10.1038/ejhg.2014.220. Epub 2014 Oct 22.

PubMed [citation]

PMID:: 25335493
PMCID:: PMC4463507

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

See all PubMed Citations (12)

Details of each submission

From GeneDx, SCV000808286.4

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

Description

Observed with a second LZTR1 variant on the opposite allele (in trans) in an individual with autosomal recessive Noonan syndrome (Johnston et al., 2018); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25480913, 27856782, 24362817, 29469822)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001249399.38

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001578236.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change creates a premature translational stop signal (p.Gln10Argfs*15) in the LZTR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LZTR1 are known to be pathogenic (PMID: 24362817, 25335493, 25480913, 25795793, 29469822, 30368668, 30442762, 30442766, 30481304, 30859559). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with Noonan syndrome or schwannomatosis (PMID: 24362817, 25480913, 29469822). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143931). 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, SCV006318388.1

#	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

From Dasa, SCV007601957.1

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

Description

NM_006767.4(LZTR1):c.27del (p.Gln10Argfs*15) is a frameshift variant in LZTR1 predicted to alter the reading frame and introduce a premature termination codon and is predicted to result in an absent or altered protein product. Loss of function is an established disease mechanism for LZTR1-associated disorders. This variant has been reported in individuals with LZTR1-related disorders (PMID: 29469822). Published studies describe this variant in association with related phenotype (PMID: 24362817; PMID: 25480913; PMID: 29469822). Also, this variant is rare in population databases. Based on the currently available evidence, this variant is 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

Last Updated: Jun 20, 2026

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