NM_152564.5(VPS13B):c.4259del (p.Gln1420fs) AND Cohen syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Sep 1, 2023
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:: RCV000050075.8

Allele description [Variation Report for NM_152564.5(VPS13B):c.4259del (p.Gln1420fs)]

NM_152564.5(VPS13B):c.4259del (p.Gln1420fs)

Gene:

VPS13B:vacuolar protein sorting 13 homolog B [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q22.2

Genomic location:

Preferred name:

NM_152564.5(VPS13B):c.4259del (p.Gln1420fs)

HGVS:

NC_000008.11:g.99511138del
NG_007098.2:g.502873del
NM_017890.5:c.4334del
NM_152564.5:c.4259delMANE SELECT
NP_060360.3:p.Gln1445fs
NP_689777.3:p.Gln1420fs
LRG_351:g.502873del
NC_000008.10:g.100523366del
NM_017890.4:c.4334delA

Protein change:

Q1420fs

Links:

dbSNP: rs386834084

NCBI 1000 Genomes Browser:

rs386834084

Molecular consequence:

NM_017890.5:c.4334del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152564.5:c.4259del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cohen syndrome (COH1)
Synonyms:: PEPPER SYNDROME; Cutis verticis gyrata, retinitis pigmentosa, and sensorineural deafness
Identifiers:: MONDO: MONDO:0008999; MedGen: C0265223; Orphanet: 193; OMIM: 216550

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000082484	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	Likely pathogenic	unknown	not provided
SCV000795083	Counsyl	no assertion criteria provided	Likely pathogenic (Oct 26, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002121149	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 1, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15141358, 16648375, 20461111, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000082484

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

no assertion criteria provided

Likely pathogenic

unknown

not provided

SCV000795083

Counsyl

no assertion criteria provided

Likely pathogenic
(Oct 26, 2017)

unknown

clinical testing

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

SCV002121149

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 1, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.

Kolehmainen J, Wilkinson R, Lehesjoki AE, Chandler K, Kivitie-Kallio S, Clayton-Smith J, Träskelin AL, Waris L, Saarinen A, Khan J, Gross-Tsur V, Traboulsi EI, Warburg M, Fryns JP, Norio R, Black GC, Manson FD.

Am J Hum Genet. 2004 Jul;75(1):122-7. Epub 2004 May 12.

PubMed [citation]

PMID:: 15141358
PMCID:: PMC1181995

Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome.

Seifert W, Holder-Espinasse M, Spranger S, Hoeltzenbein M, Rossier E, Dollfus H, Lacombe D, Verloes A, Chrzanowska KH, Maegawa GH, Chitayat D, Kotzot D, Huhle D, Meinecke P, Albrecht B, Mathijssen I, Leheup B, Raile K, Hennies HC, Horn D.

J Med Genet. 2006 May;43(5):e22.

PubMed [citation]

PMID:: 16648375
PMCID:: PMC2564527

See all PubMed Citations (4)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082484.2

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

Description

Converted during submission from probable-pathogenic to Likely pathogenic.

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

From Counsyl, SCV000795083.2

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

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	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, SCV002121149.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 56662). This premature translational stop signal has been observed in individual(s) with clinical features of Cohen syndrome (PMID: 15141358). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1445Argfs*7) in the VPS13B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in VPS13B are known to be pathogenic (PMID: 15141358, 16648375, 20461111).

#	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: Jul 5, 2025

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