NM_058246.4(DNAJB6):c.279C>A (p.Phe93Leu) AND Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 13, 2022
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:: RCV000024241.10

Allele description [Variation Report for NM_058246.4(DNAJB6):c.279C>A (p.Phe93Leu)]

NM_058246.4(DNAJB6):c.279C>A (p.Phe93Leu)

Gene:

DNAJB6:DnaJ heat shock protein family (Hsp40) member B6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q36.3

Genomic location:

Preferred name:

NM_058246.4(DNAJB6):c.279C>A (p.Phe93Leu)

Other names:

DNAJB6, PHE93LEU, 279C-A

HGVS:

NC_000007.14:g.157367416C>A
NG_032573.1:g.35401C>A
NM_001363676.1:c.279C>A
NM_005494.3:c.279C>A
NM_058246.4:c.279C>AMANE SELECT
NP_001350605.1:p.Phe93Leu
NP_005485.1:p.Phe93Leu
NP_490647.1:p.Phe93Leu
NC_000007.13:g.157160110C>A
NM_005494.2:c.279C>A
NM_058246.3:c.279C>A
O75190:p.Phe93Leu

Protein change:

F93L; PHE93LEU

Links:

UniProtKB: O75190#VAR_067834; OMIM: 611332.0004; dbSNP: rs149278319

NCBI 1000 Genomes Browser:

rs149278319

Molecular consequence:

NM_001363676.1:c.279C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005494.3:c.279C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_058246.4:c.279C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (LGMDD1)
Synonyms:: MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 1D; Autosomal dominant limb-girdle muscular dystrophy type 1D; MUSCULAR DYSTROPHY, AUTOSOMAL DOMINANT, WITH RIMMED VACUOLES; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0021018; MedGen: C4721885; Orphanet: 34516; OMIM: 603511

Recent activity

Clear Turn Off Turn On

DC007706 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus lae...
DC007706 Osada Taira anterior endomesoderm (AEM) pCS105 cDNA library Xenopus laevis cDNA clone rxlk115k20ex 3', mRNA sequence
gi|118920732|gnl|dbEST|43237539|dbj 7706.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045532	OMIM	no assertion criteria provided	Pathogenic (Feb 26, 2012)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002190198	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22334415, 26205529, 26847086, 28794355, 30564623, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045532

OMIM

no assertion criteria provided

Pathogenic
(Feb 26, 2012)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002190198

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations affecting the cytoplasmic functions of the co-chaperone DNAJB6 cause limb-girdle muscular dystrophy.

Sarparanta J, Jonson PH, Golzio C, Sandell S, Luque H, Screen M, McDonald K, Stajich JM, Mahjneh I, Vihola A, Raheem O, Penttilä S, Lehtinen S, Huovinen S, Palmio J, Tasca G, Ricci E, Hackman P, Hauser M, Katsanis N, Udd B.

Nat Genet. 2012 Feb 26;44(4):450-5, S1-2. doi: 10.1038/ng.1103.

PubMed [citation]

PMID:: 22366786
PMCID:: PMC3315599

Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy.

Harms MB, Sommerville RB, Allred P, Bell S, Ma D, Cooper P, Lopate G, Pestronk A, Weihl CC, Baloh RH.

Ann Neurol. 2012 Mar;71(3):407-16. doi: 10.1002/ana.22683. Epub 2012 Feb 14.

PubMed [citation]

PMID:: 22334415
PMCID:: PMC3314127

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000045532.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 8 affected individuals of an Italian family with limb-girdle muscular dystrophy type 1E (LGMDD1; 603511), Sarparanta et al. (2012) identified a heterozygous 279C-A transversion in exon 5 of the DNAJB6 gene, resulting in a phe93-to-leu (F93L) substitution at a highly conserved residue in the G/F domain. The F93L substitution can also be caused by a 277T-C transition (611332.0001) and a 279C-G transversion (611332.0003). The mutation was not found in 202 Finnish, 104 Italian, or 215 U.S. control individuals.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002190198.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DNAJB6 protein function. ClinVar contains an entry for this variant (Variation ID: 31530). This missense change has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 22334415, 26205529, 26847086, 28794355, 30564623). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 93 of the DNAJB6 protein (p.Phe93Leu).

#	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

ClinVar

Relating variation to medicine