NM_006767.4(LZTR1):c.370GTC[1] (p.Val125del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 20, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000997873.31

Allele description [Variation Report for NM_006767.4(LZTR1):c.370GTC[1] (p.Val125del)]

NM_006767.4(LZTR1):c.370GTC[1] (p.Val125del)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

22q11.21

Genomic location:

Preferred name:

NM_006767.4(LZTR1):c.370GTC[1] (p.Val125del)

HGVS:

NC_000022.11:g.20987553GTC[1]
NC_000022.11:g.20987553_20987555GTC[1]
NG_034193.1:g.10285GTC[1]
NM_006767.4:c.370GTC[1]MANE SELECT
NP_006758.2:p.Val125del
LRG_989t1:c.370GTC[1]
LRG_989:g.10285GTC[1]
LRG_989p1:p.Val125del
NC_000022.10:g.21341841_21341843del
NC_000022.10:g.21341842GTC[1]
NM_006767.3:c.373_375del
NM_006767.3:c.373_375delGTC
NM_006767.4:c.373_375delMANE SELECT

Protein change:

V125del

Links:

dbSNP: rs755783378

NCBI 1000 Genomes Browser:

rs755783378

Molecular consequence:

NM_006767.4:c.370GTC[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001153627	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Feb 1, 2019)	germline	clinical testing	Citation Link,
SCV001987713	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Sep 20, 2024)	germline	clinical testing	Citation Link,
SCV002985337	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25335493, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001153627

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Feb 1, 2019)

germline

clinical testing

Citation Link,

SCV001987713

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Sep 20, 2024)

germline

clinical testing

Citation Link,

SCV002985337

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 3, 2023)

germline

clinical testing

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	yes	1	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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001153627.27

#	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 GeneDx, SCV001987713.5

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

Description

In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25335493, 30368668, 27921248, 30481304)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002985337.2

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

Description

This variant, c.373_375del, results in the deletion of 1 amino acid(s) of the LZTR1 protein (p.Val125del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755783378, gnomAD 0.007%). This variant has been observed in individual(s) with clinical features of schwannomatosis (PMID: 25335493). ClinVar contains an entry for this variant (Variation ID: 809328). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine