NM_001927.4(DES):c.17C>G (p.Ser6Trp) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 12, 2021
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:: RCV002407124.2

Allele description [Variation Report for NM_001927.4(DES):c.17C>G (p.Ser6Trp)]

NM_001927.4(DES):c.17C>G (p.Ser6Trp)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.17C>G (p.Ser6Trp)

HGVS:

NC_000002.12:g.219418479C>G
NG_008043.1:g.5103C>G
NG_046330.1:g.18871C>G
NM_001382708.1:c.17C>G
NM_001382709.1:c.17C>G
NM_001382710.1:c.17C>G
NM_001382711.1:c.17C>G
NM_001382712.1:c.17C>G
NM_001382713.1:c.17C>G
NM_001927.4:c.17C>GMANE SELECT
NP_001369637.1:p.Ser6Trp
NP_001369638.1:p.Ser6Trp
NP_001369639.1:p.Ser6Trp
NP_001369640.1:p.Ser6Trp
NP_001369641.1:p.Ser6Trp
NP_001369642.1:p.Ser6Trp
NP_001918.3:p.Ser6Trp
LRG_380t1:c.17C>G
LRG_380:g.5103C>G
NC_000002.11:g.220283201C>G
NM_001927.3:c.17C>G

Protein change:

S6W

Links:

dbSNP: rs1214936508

NCBI 1000 Genomes Browser:

rs1214936508

Molecular consequence:

NM_001382708.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382709.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382710.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382711.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382712.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382713.1:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001927.4:c.17C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002717294	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 12, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25557463, 33546848 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002717294

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 12, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Autophagic vacuolar pathology in desminopathies.

Weihl CC, Iyadurai S, Baloh RH, Pittman SK, Schmidt RE, Lopate G, Pestronk A, Harms MB.

Neuromuscul Disord. 2015 Mar;25(3):199-206. doi: 10.1016/j.nmd.2014.12.002. Epub 2014 Dec 12.

PubMed [citation]

PMID:: 25557463
PMCID:: PMC4355324

Desminopathy presenting as late onset bilateral facial weakness, with diagnosis supported by lower limb MRI.

Carroll LS, Walker M, Allen D, Marini-Bettolo C, Ditchfield A, Pinto AA, Hammans SR.

Neuromuscul Disord. 2021 Mar;31(3):249-252. doi: 10.1016/j.nmd.2020.12.013. Epub 2021 Jan 8.

PubMed [citation]

PMID:: 33546848

Details of each submission

From Ambry Genetics, SCV002717294.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.S6W variant (also known as c.17C>G), located in coding exon 1 of the DES gene, results from a C to G substitution at nucleotide position 17. The serine at codon 6 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant was initially reported in an individual with dilated cardiomyopathy (DCM) and progressive myopathy and was also detected in his similarly affected father (Weihl CC et al. Neuromuscul Disord, 2015 Mar;25:199-206). This variant has also been described in an individual with progressive facial weakness and mild left ventricular hypertrophy (Carroll LS et al. Neuromuscul Disord, 2021 03;31:249-252). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

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