NM_000248.3(MITF):c.637G>C (p.Glu213Gln) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Jul 6, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description

NM_000248.3(MITF):c.637G>C (p.Glu213Gln)

MITF:melanocyte inducing transcription factor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000248.3(MITF):c.637G>C (p.Glu213Gln)
  • NC_000003.12:g.69956457G>C
  • NG_011631.1:g.221976G>C
  • NM_000248.3:c.637G>C
  • NP_000239.1:p.Glu213Gln
  • LRG_776t1:c.637G>C
  • LRG_776:g.221976G>C
  • LRG_776p1:p.Glu213Gln
  • NC_000003.11:g.70005608G>C
Protein change:
dbSNP: rs1057522775
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000248.3:c.637G>C - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000529405GeneDxcriteria provided, single submitter
Likely pathogenic
(Jul 6, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000529405.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The E213Q variant in the MITF gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The E213Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E213Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue, E213D, has been reported as a de novo event in a patient with Waardenburg syndrome type 2A (Leger et al., 2012). In addition, missense variants in nearby residues (N210K, I212S, I212M, R216K, R217G, R217I) have been reported in the Human Gene Mutation Database in association with MITF-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. The E213Q variant is a strong candidate for a pathogenic variant, consistent with the congenital sensorineural hearing loss, ocular albinism, nystagmus, retinal pigmentary changes, hypopigmentation, and patchy hyperpigmented skin macules reported. However the possibility it may be a rare benign variant cannot be excluded.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 18, 2018