NM_001927.4(DES):c.35C>T (p.Ser12Phe) AND Desmin-related myofibrillar myopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 3, 2024
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:: RCV001061421.9

Allele description [Variation Report for NM_001927.4(DES):c.35C>T (p.Ser12Phe)]

NM_001927.4(DES):c.35C>T (p.Ser12Phe)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.35C>T (p.Ser12Phe)

HGVS:

NC_000002.12:g.219418497C>T
NG_008043.1:g.5121C>T
NG_046330.1:g.18889C>T
NM_001927.4:c.35C>TMANE SELECT
NP_001918.3:p.Ser12Phe
LRG_380t1:c.35C>T
LRG_380:g.5121C>T
NC_000002.11:g.220283219C>T
NM_001927.3:c.35C>T

Protein change:

S12F

Links:

dbSNP: rs267607495

NCBI 1000 Genomes Browser:

rs267607495

Molecular consequence:

NM_001927.4:c.35C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Desmin-related myofibrillar myopathy (MFM1)
Synonyms:: Desminopathy; Desmin related myopathy (former name); Desmin storage myopathy (former name); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011076; MedGen: C1832370; Orphanet: 363543; Orphanet: 98909; OMIM: 601419

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001226164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 16, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20696008, 28492532
SCV005091060	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 3, 2024)	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

SCV001226164

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 16, 2021)

germline

clinical testing

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

SCV005091060

Laboratory of Medical Genetics, National & Kapodistrian University of Athens

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 3, 2024)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene.

Hong D, Wang Z, Zhang W, Xi J, Lu J, Luan X, Yuan Y.

Neuropathol Appl Neurobiol. 2011 Apr;37(3):257-70. doi: 10.1111/j.1365-2990.2010.01112.x.

PubMed [citation]

PMID:: 20696008

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001226164.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has been reported to affect DES protein function (PMID: 20696008). This variant has been observed to segregate with desminopathy in an affected family (PMID: 20696008) and has been observed to be de novo in an individual with clinical features consistent with DES-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 66412). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with phenylalanine at codon 12 of the DES protein (p.Ser12Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine.

#	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 Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV005091060.1

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

Description

PM1, PM2, PP2, PP3, PP5 - Low frequency in gnomAD population databases. Low frequency in gnomAD population databases. This variant has been previously reported as causative for desminopathy. (PMID:23143191).

#	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: Sep 29, 2024

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