NM_004415.4(DSP):c.5707C>A (p.Gln1903Lys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 15, 2020
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:: RCV000554349.7

Allele description [Variation Report for NM_004415.4(DSP):c.5707C>A (p.Gln1903Lys)]

NM_004415.4(DSP):c.5707C>A (p.Gln1903Lys)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.5707C>A (p.Gln1903Lys)

Other names:

p.Q1903K:CAA>AAA

HGVS:

NC_000006.12:g.7582969C>A
NG_008803.1:g.46333C>A
NM_001008844.3:c.3910C>A
NM_001319034.2:c.4378C>A
NM_004415.4:c.5707C>AMANE SELECT
NP_001008844.1:p.Gln1304Lys
NP_001305963.1:p.Gln1460Lys
NP_004406.2:p.Gln1903Lys
LRG_423t1:c.5707C>A
LRG_423:g.46333C>A
NC_000006.11:g.7583202C>A
NM_004415.2:c.5707C>A

Protein change:

Q1304K

Links:

dbSNP: rs794728103

NCBI 1000 Genomes Browser:

rs794728103

Molecular consequence:

NM_001008844.3:c.3910C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.4378C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.5707C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Arrhythmogenic cardiomyopathy with wooly hair and keratoderma
Synonyms:: Palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair; Epidermolytic palmoplantar keratoderma woolly hair and dilated cardiomyopathy; Dilated cardiomyopathy with woolly hair and keratoderma; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011581; MedGen: C1854063; Orphanet: 65282; OMIM: 605676

Name:: Arrhythmogenic right ventricular dysplasia 8 (ARVD8)
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 8; Arrhythmogenic right ventricular cardiomyopathy, type 8; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 8
Identifiers:: MONDO: MONDO:0011831; MedGen: C1843896; OMIM: 607450

Recent activity

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guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X1 [Ho...
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 isoform X1 [Homo sapiens]
gi|2462568819|ref|XP_054178663.1|

Protein
Priestia aryabhattai strain:IIRRPSB13
Priestia aryabhattai strain:IIRRPSB13
Priestia aryabhattai strain:IIRRPSB13 | isolate:IIRRPSB13 Genome sequencing and assembly

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000641324	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 15, 2020)	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

SCV000641324

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 15, 2020)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000641324.4

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

Description

In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 199843). This sequence change replaces glutamine with lysine at codon 1903 of the DSP protein (p.Gln1903Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine