NM_004415.4(DSP):c.3146C>T (p.Ser1049Leu) AND Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 13, 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:: RCV003995896.2

Allele description [Variation Report for NM_004415.4(DSP):c.3146C>T (p.Ser1049Leu)]

NM_004415.4(DSP):c.3146C>T (p.Ser1049Leu)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.3146C>T (p.Ser1049Leu)

HGVS:

NC_000006.12:g.7579336C>T
NG_008803.1:g.42700C>T
NM_001008844.3:c.3146C>T
NM_001319034.2:c.3146C>T
NM_004415.4:c.3146C>TMANE SELECT
NP_001008844.1:p.Ser1049Leu
NP_001305963.1:p.Ser1049Leu
NP_004406.2:p.Ser1049Leu
LRG_423t1:c.3146C>T
LRG_423:g.42700C>T
NC_000006.11:g.7579569C>T
NM_004415.2:c.3146C>T

Protein change:

S1049L

Links:

dbSNP: rs751361395

NCBI 1000 Genomes Browser:

rs751361395

Molecular consequence:

NM_001008844.3:c.3146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.3146C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.3146C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

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RecName: Full=Small ribosomal subunit protein uS15c; AltName: Full=30S ribosomal...
RecName: Full=Small ribosomal subunit protein uS15c; AltName: Full=30S ribosomal protein S15, chloroplastic
gi|215274997|sp|A4QKZ1.1|RR15_CRUWA

Protein
RecName: Full=NAD(P)H-quinone oxidoreductase subunit 6, chloroplastic; AltName: ...
RecName: Full=NAD(P)H-quinone oxidoreductase subunit 6, chloroplastic; AltName: Full=NAD(P)H dehydrogenase subunit 6; AltName: Full=NADH-plastoquinone oxidoreductase subunit 6
gi|221272318|sp|A4QKY7.1|NU6C_CRUWA

Protein
Chain F, Histone H3.1
Chain F, Histone H3.1
gi|2748787162|pdb|8KCB|F

Protein
Chain D, Histone H2B.10
Chain D, Histone H2B.10
gi|2748787178|pdb|8KCC|D

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004822070	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 13, 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

SCV004822070

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 13, 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	14	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004822070.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	14	not provided	not provided	clinical testing	PubMed (1)

Description

This missense variant replaces serine with leucine at codon 1049 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 27/282260 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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	108544	not provided	not provided		14	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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