NM_004415.4(DSP):c.5972T>C (p.Leu1991Ser) AND Arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 26, 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:: RCV004009574.2

Allele description [Variation Report for NM_004415.4(DSP):c.5972T>C (p.Leu1991Ser)]

NM_004415.4(DSP):c.5972T>C (p.Leu1991Ser)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.5972T>C (p.Leu1991Ser)

HGVS:

NC_000006.12:g.7583234T>C
NG_008803.1:g.46598T>C
NM_001008844.3:c.4175T>C
NM_001319034.2:c.4643T>C
NM_004415.4:c.5972T>CMANE SELECT
NP_001008844.1:p.Leu1392Ser
NP_001305963.1:p.Leu1548Ser
NP_004406.2:p.Leu1991Ser
NP_004406.2:p.Leu1991Ser
LRG_423t1:c.5972T>C
LRG_423:g.46598T>C
LRG_423p1:p.Leu1991Ser
NC_000006.11:g.7583467T>C
NM_004415.2:c.5972T>C

Protein change:

L1392S

Molecular consequence:

NM_001008844.3:c.4175T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.4643T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.5972T>C - 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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polycomb protein Suz12 isoform 1 [Mus musculus]
polycomb protein Suz12 isoform 1 [Mus musculus]
gi|40353214|ref|NP_954666.1|

Protein
uncharacterized protein LOC103499390 [Cucumis melo]
uncharacterized protein LOC103499390 [Cucumis melo]
gi|659121346|ref|XP_008460612.1|

Protein
inactive protein kinase SELMODRAFT_444075-like isoform X1 [Cucurbita moschata]
inactive protein kinase SELMODRAFT_444075-like isoform X1 [Cucurbita moschata]
gi|1279767513|ref|XP_022936305.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004830957	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jun 26, 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

SCV004830957

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jun 26, 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	1	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, SCV004830957.1

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

Description

This missense variant replaces leucine with serine at codon 1991 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 DSP-related disorders in the literature. This variant has been identified in 2/251432 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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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