NM_001289104.2(PRKCSH):c.841C>T (p.Arg281Trp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 17, 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:: RCV002539633.4

Allele description [Variation Report for NM_001289104.2(PRKCSH):c.841C>T (p.Arg281Trp)]

NM_001289104.2(PRKCSH):c.841C>T (p.Arg281Trp)

Gene:

PRKCSH:PRKCSH beta subunit of glucosidase II [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.2

Genomic location:

Preferred name:

NM_001289104.2(PRKCSH):c.841C>T (p.Arg281Trp)

HGVS:

NC_000019.10:g.11447152C>T
NG_009300.1:g.16699C>T
NM_001001329.3:c.841C>T
NM_001289102.2:c.841C>T
NM_001289103.2:c.841C>T
NM_001289104.2:c.841C>TMANE SELECT
NM_001379608.1:c.841C>T
NM_001379609.1:c.841C>T
NM_002743.3:c.841C>T
NP_001001329.1:p.Arg281Trp
NP_001276031.1:p.Arg281Trp
NP_001276032.1:p.Arg281Trp
NP_001276033.1:p.Arg281Trp
NP_001366537.1:p.Arg281Trp
NP_001366538.1:p.Arg281Trp
NP_002734.2:p.Arg281Trp
NC_000019.9:g.11557967C>T

Protein change:

R281W

Links:

dbSNP: rs746231889

NCBI 1000 Genomes Browser:

rs746231889

Molecular consequence:

NM_001001329.3:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289102.2:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289103.2:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001289104.2:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379608.1:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379609.1:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002743.3:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003442875	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 14, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004028316	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Feb 17, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442875

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 14, 2022)

germline

clinical testing

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

SCV004028316

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Feb 17, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003442875.2

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1255532). This variant has not been reported in the literature in individuals affected with PRKCSH-related conditions. This variant is present in population databases (rs746231889, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 281 of the PRKCSH protein (p.Arg281Trp).

#	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 GeneDx, SCV004028316.1

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

Description

Identified in a patient with polycystic liver disease in published literature (van de Laarschot et al., 2020); patient-level information not provided; Reported in one patient and mother with polycystic liver disease in published literature (Peces et a l., 2005); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 16437702, 33097077)

#	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

Last Updated: Sep 29, 2024

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