NM_152564.5(VPS13B):c.11809A>G (p.Lys3937Glu) AND Cohen syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 20, 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:: RCV003849425.1

Allele description [Variation Report for NM_152564.5(VPS13B):c.11809A>G (p.Lys3937Glu)]

NM_152564.5(VPS13B):c.11809A>G (p.Lys3937Glu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

8q22.2

Genomic location:

Preferred name:

NM_152564.5(VPS13B):c.11809A>G (p.Lys3937Glu)

HGVS:

NC_000008.11:g.99875481A>G
NG_007098.2:g.867216A>G
NM_017890.5:c.11884A>G
NM_152564.5:c.11809A>GMANE SELECT
NP_060360.3:p.Lys3962Glu
NP_060360.3:p.Lys3962Glu
NP_689777.3:p.Lys3937Glu
NP_689777.3:p.Lys3937Glu
LRG_351t1:c.11884A>G
LRG_351t2:c.11809A>G
LRG_351:g.867216A>G
LRG_351p1:p.Lys3962Glu
LRG_351p2:p.Lys3937Glu
NC_000008.10:g.100887709A>G
NM_017890.4:c.11884A>G
NM_152564.4:c.11809A>G

Protein change:

K3937E

Molecular consequence:

NM_017890.5:c.11884A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_152564.5:c.11809A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV004650711	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 20, 2023)	germline	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

SCV004650711

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 20, 2023)

germline

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

Citations

PubMed

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 Invitae, SCV004650711.1

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on VPS13B protein function. This variant has not been reported in the literature in individuals affected with VPS13B-related conditions. This variant is present in population databases (rs755070874, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 3962 of the VPS13B protein (p.Lys3962Glu).

#	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: Mar 5, 2024

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