NM_005211.3(CSF1R):c.2624T>C (p.Met875Thr)

NM_005211.3(CSF1R):c.2624T>C (p.Met875Thr)

Variant type:
single nucleotide variant
Cytogenetic location:
5q32
Genomic location:
  • Chr5:149434830 (on Assembly GRCh37)
  • Chr5:150055267 (on Assembly GRCh38)
Protein change:
M875T
HGVS:
  • NG_012303.1:g.63106T>C
  • NM_005211.3:c.2624T>C
  • NC_000005.10:g.150055267A>G (GRCh38)
  • NC_000005.9:g.149434830A>G (GRCh37)
  • NP_005202.2:p.Met875Thr
Links:
NCBI 1000 Genomes Browser:
rs281860279
Molecular consequence:
  • NM_005211.3:c.2624T>C: missense variant SO:0001583
  • NR_109969.1:n.2674T>C: non-coding transcript variant SO:0001619

Clinical significance

NM_005211.3(CSF1R):c.2624T>C (p.Met875Thr)

Clinical significance:
Pathogenic/Likely pathogenic
Review status:
2 stars out of maximum of 4 stars
classified by multiple submitters
Number of submission(s):
2
Condition(s)
See supporting ClinVar records

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Recent Activity

Assertion and evidence details

Germline

Clinical significance
(Last evaluated)
Review status
(Assertion method)
Collection methodCondition(s)
(Mode of inheritance)
OriginCitationsSubmitter
(Last submitted)
Submission accession
Pathogenic
(Nov 13, 2014)
classified by single submitter
(literature only)
literature onlygermlinePubMed (2)
OMIM
(Mar 14, 2012)
SCV000043973
Pathogenic
(Aug 30, 2012)
classified by single submitter
(literature only)
literature onlynot providedPubMed (1)
GeneReviews
(Nov 29, 2012)
SCV000054591

Summary

FamiliesIndividualsSegregationAllele originEthnicityGeographic origin
not providednot providednot providedgermline, not providednot providednot provided

GeneReviews

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providednot provided

OMIM

Data published from literature

FamiliesIndividualsSegregationsAllele originCitations
not providednot providednot providedgermline

Description

In affected members of a large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820) originally reported by Swerdlow et al. (2009), Rademakers et al. (2011) identified a heterozygous 2624T-C transition in exon 20 of the CSF1R gene, resulting in a met875-to-thr (M875T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers.
In affected members of a large family with hereditary diffuse leukoencephalopathy with spheroids (HDLS; 221820) originally reported by Swerdlow et al. (2009), Rademakers et al. (2012) identified a heterozygous 2624T-C transition in exon 20 of the CSF1R gene, resulting in a met875-to-thr (M875T) substitution in a highly conserved residue in the intracellular tyrosine kinase domain. The mutation was not found in 1,436 controls. In vitro functional expression studies indicated that the mutant protein did not show autophosphorylation, suggesting a defect in kinase activity that likely also affects downstream targets. The mutant protein probably also acts in a dominant-negative manner, since CSF1R assembles into homodimers.

Last Updated: Jan 13, 2015

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