NM_000081.4(LYST):c.5491C>T (p.Gln1831Ter) AND Chédiak-Higashi syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 7, 2023
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:: RCV001925907.5

Allele description [Variation Report for NM_000081.4(LYST):c.5491C>T (p.Gln1831Ter)]

NM_000081.4(LYST):c.5491C>T (p.Gln1831Ter)

Gene:

LYST:lysosomal trafficking regulator [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.3

Genomic location:

Preferred name:

NM_000081.4(LYST):c.5491C>T (p.Gln1831Ter)

HGVS:

NC_000001.11:g.235775056G>A
NG_007397.1:g.113585C>T
NM_000081.4:c.5491C>TMANE SELECT
NM_001301365.1:c.5491C>T
NP_000072.2:p.Gln1831Ter
NP_001288294.1:p.Gln1831Ter
LRG_143t2:c.5491C>T
LRG_143:g.113585C>T
LRG_143p2:p.Gln1831Ter
NC_000001.10:g.235938356G>A

Protein change:

Q1831*

Molecular consequence:

NM_000081.4:c.5491C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001301365.1:c.5491C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Chédiak-Higashi syndrome (CHS)
Synonyms:: Chediak-Higashi Syndrome
Identifiers:: MONDO: MONDO:0008963; MedGen: C0007965; Orphanet: 167; OMIM: 214500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002180060	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 14, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9215679, 11857544, 28492532
SCV004191171	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 7, 2023)	unknown	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

SCV002180060

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 14, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004191171

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 7, 2023)

unknown

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	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

Mutations in the Chediak-Higashi syndrome gene (CHS1) indicate requirement for the complete 3801 amino acid CHS protein.

Karim MA, Nagle DL, Kandil HH, Bürger J, Moore KJ, Spritz RA.

Hum Mol Genet. 1997 Jul;6(7):1087-9.

PubMed [citation]

PMID:: 9215679

Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome.

Karim MA, Suzuki K, Fukai K, Oh J, Nagle DL, Moore KJ, Barbosa E, Falik-Borenstein T, Filipovich A, Ishida Y, Kivrikko S, Klein C, Kreuz F, Levin A, Miyajima H, Regueiro JR, Russo C, Uyama E, Vierimaa O, Spritz RA.

Am J Med Genet. 2002 Feb 15;108(1):16-22.

PubMed [citation]

PMID:: 11857544

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002180060.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with LYST-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln1831*) in the LYST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LYST are known to be pathogenic (PMID: 9215679, 11857544).

#	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 Baylor Genetics, SCV004191171.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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