NM_001354604.2(MITF):c.1213T>C (p.Ser405Pro) AND Waardenburg syndrome type 2A

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 1, 2000
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:: RCV000015347.29

Allele description [Variation Report for NM_001354604.2(MITF):c.1213T>C (p.Ser405Pro)]

NM_001354604.2(MITF):c.1213T>C (p.Ser405Pro)

Gene:

MITF:melanocyte inducing transcription factor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p13

Genomic location:

Preferred name:

NM_001354604.2(MITF):c.1213T>C (p.Ser405Pro)

HGVS:

NC_000003.12:g.69964880T>C
NG_011631.1:g.230399T>C
NM_000248.4:c.892T>C
NM_001184967.2:c.1039T>C
NM_001354604.2:c.1213T>CMANE SELECT
NM_001354605.2:c.1210T>C
NM_001354606.2:c.1192T>C
NM_001354607.2:c.1144T>C
NM_001354608.2:c.1039T>C
NM_006722.3:c.1192T>C
NM_198158.3:c.874T>C
NM_198159.3:c.1195T>C
NM_198177.3:c.1147T>C
NM_198178.3:c.706T>C
NP_000239.1:p.Ser298Pro
NP_000239.1:p.Ser298Pro
NP_001171896.1:p.Ser347Pro
NP_001341533.1:p.Ser405Pro
NP_001341534.1:p.Ser404Pro
NP_001341535.1:p.Ser398Pro
NP_001341536.1:p.Ser382Pro
NP_001341537.1:p.Ser347Pro
NP_006713.1:p.Ser398Pro
NP_937801.1:p.Ser292Pro
NP_937802.1:p.Ser399Pro
NP_937820.1:p.Ser383Pro
NP_937821.2:p.Ser236Pro
LRG_776t1:c.892T>C
LRG_776:g.230399T>C
LRG_776p1:p.Ser298Pro
NC_000003.11:g.70014031T>C
NM_000248.3:c.892T>C

Protein change:

S236P; SER298PRO

Links:

OMIM: 156845.0008; dbSNP: rs104893747

NCBI 1000 Genomes Browser:

rs104893747

Molecular consequence:

NM_000248.4:c.892T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.1039T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.1213T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.1210T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.1192T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.1144T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.1039T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.1192T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.874T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.1195T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.1147T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.706T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Waardenburg syndrome type 2A (WS2A)
Synonyms:: WAARDENBURG SYNDROME WITHOUT DYSTOPIA CANTHORUM
Identifiers:: MONDO: MONDO:0008671; MedGen: C1860339; Orphanet: 3440; OMIM: 193510

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000035606	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2000)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8589691, 10587587

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000035606

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2000)

germline

literature only

PubMed (2)
[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

Citations

PubMed

The mutational spectrum in Waardenburg syndrome.

Tassabehji M, Newton VE, Liu XZ, Brady A, Donnai D, Krajewska-Walasek M, Murday V, Norman A, Obersztyn E, Reardon W, et al.

Hum Mol Genet. 1995 Nov;4(11):2131-7.

PubMed [citation]

PMID:: 8589691

Ser298 of MITF, a mutation site in Waardenburg syndrome type 2, is a phosphorylation site with functional significance.

Takeda K, Takemoto C, Kobayashi I, Watanabe A, Nobukuni Y, Fisher DE, Tachibana M.

Hum Mol Genet. 2000 Jan 1;9(1):125-32.

PubMed [citation]

PMID:: 10587587

Details of each submission

From OMIM, SCV000035606.4

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

Description

Tassabehji et al. (1995) found that affected members of a family with type 2 Waardenburg syndrome (WS2A; 193510) had a ser298-to-pro substitution in their MITF gene. Takeda et al. (2000) showed that ser298, which is located downstream of the basic helix-loop-helix leucine zipper, plays an important role in MITF function. They found that glycogen synthase kinase-3 (GSK3) phosphorylated ser298 in vitro, thereby enhancing the binding of MITF to the tyrosinase promoter. The same serine was found to be phosphorylated in vivo, and expression of dominant-negative GSK3-beta selectively suppressed the ability of MITF to transactivate the tyrosinase promoter. Moreover, mutation of ser298 disabled phosphorylation of MITF by GSK3-beta and impaired MITF function.

#	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

Last Updated: Oct 13, 2024

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