NM_001942.4(DSG1):c.382C>T (p.Arg128Ter) AND not provided

Germline classification:: Pathogenic (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:: RCV003740031.3

Allele description [Variation Report for NM_001942.4(DSG1):c.382C>T (p.Arg128Ter)]

NM_001942.4(DSG1):c.382C>T (p.Arg128Ter)

Gene:

DSG1:desmoglein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q12.1

Genomic location:

Preferred name:

NM_001942.4(DSG1):c.382C>T (p.Arg128Ter)

HGVS:

NC_000018.10:g.31329901C>T
NG_011803.2:g.16813C>T
NG_138591.1:g.259C>T
NM_001942.2:c.382C>T
NM_001942.4:c.382C>TMANE SELECT
NP_001933.2:p.Arg128Ter
NC_000018.9:g.28909864C>T

Protein change:

R128*

Molecular consequence:

NM_001942.4:c.382C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004551772	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 19018793, 23974871, 27534273, 27632246, 29604126, 33539609, 28492532
SCV005327585	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004551772

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV005327585

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 10, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel mutations in DSG1 causing striate palmoplantar keratoderma.

Hershkovitz D, Lugassy J, Indelman M, Bergman R, Sprecher E.

Clin Exp Dermatol. 2009 Mar;34(2):224-8. doi: 10.1111/j.1365-2230.2008.02733.x. Epub 2008 Nov 6.

PubMed [citation]

PMID:: 19018793

Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting.

Samuelov L, Sarig O, Harmon RM, Rapaport D, Ishida-Yamamoto A, Isakov O, Koetsier JL, Gat A, Goldberg I, Bergman R, Spiegel R, Eytan O, Geller S, Peleg S, Shomron N, Goh CSM, Wilson NJ, Smith FJD, Pohler E, Simpson MA, McLean WHI, Irvine AD, et al.

Nat Genet. 2013 Oct;45(10):1244-1248. doi: 10.1038/ng.2739. Epub 2013 Aug 25.

PubMed [citation]

PMID:: 23974871
PMCID:: PMC3791825

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004551772.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg128*) in the DSG1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSG1 are known to be pathogenic (PMID: 19018793, 23974871, 27534273, 27632246, 29604126). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with DSG1-related conditions (PMID: 33539609). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV005327585.1

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

Description

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33539609, 30451323)

#	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: Oct 8, 2024

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