NM_001366385.1(CARD14):c.536G>A (p.Arg179His) AND multiple conditions

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 19, 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:: RCV000691452.8

Allele description [Variation Report for NM_001366385.1(CARD14):c.536G>A (p.Arg179His)]

NM_001366385.1(CARD14):c.536G>A (p.Arg179His)

Gene:

CARD14:caspase recruitment domain family member 14 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_001366385.1(CARD14):c.536G>A (p.Arg179His)

HGVS:

NC_000017.11:g.80184099G>A
NG_032778.1:g.19108G>A
NM_001257970.1:c.536G>A
NM_001366385.1:c.536G>AMANE SELECT
NM_024110.4:c.536G>A
NP_001244899.1:p.Arg179His
NP_001353314.1:p.Arg179His
NP_077015.2:p.Arg179His
LRG_1330t1:c.536G>A
LRG_1330:g.19108G>A
LRG_1330p1:p.Arg179His
NC_000017.10:g.78157898G>A
NR_047566.2:n.731G>A
Q9BXL6:p.Arg179His

Protein change:

R179H

Links:

UniProtKB: Q9BXL6#VAR_068231; UniProtKB/Swiss-Prot: VAR_068231; dbSNP: rs199517469

NCBI 1000 Genomes Browser:

rs199517469

Molecular consequence:

NM_001257970.1:c.536G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001366385.1:c.536G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024110.4:c.536G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_047566.2:n.731G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Pityriasis rubra pilaris (PRP)
Synonyms:: Pityriasis rubra pilaris--familial type
Identifiers:: MONDO: MONDO:0100017; MedGen: C0032027; Orphanet: 2897; OMIM: 173200

Name:: Psoriasis 2
Identifiers:: MONDO: MONDO:0011269; MedGen: C1864497; OMIM: 602723

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000819230	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 19, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25989471, 28887889, 22521419, 28492532
SCV002788177	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2022)	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

SCV000819230

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 19, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002788177

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2022)

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	unknown	unknown	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

Palmoplantar Pustular Psoriasis Is Associated with Missense Variants in CARD14, but Not with Loss-of-Function Mutations in IL36RN in European Patients.

Mössner R, Frambach Y, Wilsmann-Theis D, Löhr S, Jacobi A, Weyergraf A, Müller M, Philipp S, Renner R, Traupe H, Burkhardt H, Kingo K, Kõks S, Uebe S, Sticherling M, Sticht H, Oji V, Hüffmeier U.

J Invest Dermatol. 2015 Oct;135(10):2538-2541. doi: 10.1038/jid.2015.186. Epub 2015 May 19. No abstract available.

PubMed [citation]

PMID:: 25989471

The genetic basis for most patients with pustular skin disease remains elusive.

Mössner R, Wilsmann-Theis D, Oji V, Gkogkolou P, Löhr S, Schulz P, Körber A, Prinz JC, Renner R, Schäkel K, Vogelsang L, Peters KP, Philipp S, Reich K, Ständer H, Jacobi A, Weyergraf A, Kingo K, Kõks S, Gerdes S, Steinz K, Schill T, et al.

Br J Dermatol. 2018 Mar;178(3):740-748. doi: 10.1111/bjd.15867. Epub 2018 Jan 22.

PubMed [citation]

PMID:: 28887889

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000819230.6

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

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 179 of the CARD14 protein (p.Arg179His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with psoriasis (PMID: 22521419, 25989471, 28887889). ClinVar contains an entry for this variant (Variation ID: 68783). 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) performed at Invitae indicates that this missense variant is expected to disrupt CARD14 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CARD14 function (PMID: 22521419). 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

From Fulgent Genetics, Fulgent Genetics, SCV002788177.1

#	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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