NM_006796.2(AFG3L2):c.1997T>G (p.Met666Arg) AND Spinocerebellar ataxia 28

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 17, 2011
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000023377.3

Allele description

NM_006796.2(AFG3L2):c.1997T>G (p.Met666Arg)

Gene:

AFG3L2:AFG3 like matrix AAA peptidase subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.21

Genomic location:

Preferred name:

NM_006796.2(AFG3L2):c.1997T>G (p.Met666Arg)

HGVS:

NC_000018.10:g.12337519A>C
NG_023361.1:g.44758T>G
NM_006796.2:c.1997T>G
NP_006787.2:p.Met666Arg
LRG_666t1:c.1997T>G
LRG_666:g.44758T>G
LRG_666p1:p.Met666Arg
NC_000018.9:g.12337518A>C
Q9Y4W6:p.Met666Arg

Protein change:

M666R; MET666ARG

Links:

UniProtKB: Q9Y4W6#VAR_064403; OMIM: 604581.0007; dbSNP: rs151344515

NCBI 1000 Genomes Browser:

rs151344515

Molecular consequence:

NM_006796.2:c.1997T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spinocerebellar ataxia 28 (SCA28)
Identifiers:: MedGen: C1853249; Orphanet: 101109; OMIM: 610246

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000044668	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2010)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000054612	GeneReviews	no assertion criteria provided	pathologic (May 17, 2011)	not provided	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000044668

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2010)

germline

literature only

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

SCV000054612

GeneReviews

no assertion criteria provided

pathologic
(May 17, 2011)

not provided

curation

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	not provided	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Missense mutations in the AFG3L2 proteolytic domain account for ∼1.5% of European autosomal dominant cerebellar ataxias.

Cagnoli C, Stevanin G, Brussino A, Barberis M, Mancini C, Margolis RL, Holmes SE, Nobili M, Forlani S, Padovan S, Pappi P, Zaros C, Leber I, Ribai P, Pugliese L, Assalto C, Brice A, Migone N, Dürr A, Brusco A.

Hum Mutat. 2010 Oct;31(10):1117-24. doi: 10.1002/humu.21342.

PubMed [citation]

PMID:: 20725928

Details of each submission

From OMIM, SCV000044668.2

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

Description

In 2 affected members a family with autosomal dominant SCA28 (610246), Cagnoli et al. (2010) identified a heterozygous 1997T-G transversion in exon 16 of the AFG3L2 gene, resulting in a met666-to-arg (M666R) substitution in a highly conserved residue in the C-terminal proteolytic peptidase-M41 domain. Met666 is located on the surface of the AFG3L2 complex, and the mutation was predicted to decrease the electrostatic potential difference between the inner mitochondrial membrane side and the matrix side of the hexameric complex, as well as decrease the central pore dipole. These findings suggested a destabilizing effect. The mutation was not identified in 380 French or Italian control chromosomes.

#	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 GeneReviews, SCV000054612.1

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

Description

Converted during submission to Pathogenic.

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

Last Updated: Dec 9, 2017

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