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

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 26, 2024
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:
RCV002513060.4

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:
Tietz syndrome (TADS)
Synonyms:
Albinism-deafness of Tietz; Hypopigmentation/deafness of Tietz; Tietz albinism-deafness syndrome
Identifiers:
MONDO: MONDO:0007077; MedGen: C0391816; Orphanet: 42665; OMIM: 103500
Name:
Waardenburg syndrome type 2A (WS2A)
Synonyms:
WAARDENBURG SYNDROME WITHOUT DYSTOPIA CANTHORUM
Identifiers:
MONDO: MONDO:0008671; MedGen: C1860339; Orphanet: 3440; OMIM: 193510
Name:
Melanoma, cutaneous malignant, susceptibility to, 8
Synonyms:
MELANOMA AND RENAL CELL CARCINOMA, SUSCEPTIBILITY TO; Cutaneous malignant melanoma 8
Identifiers:
MONDO: MONDO:0013759; MedGen: C3152204; Orphanet: 293822; OMIM: 614456

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003513183Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 26, 2024)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

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

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

Prenatal diagnosis and genetic counseling for Waardenburg syndrome type I and II in Chinese families.

Wang L, Qin L, Li T, Liu H, Ma L, Li W, Wu D, Wang H, Guo Q, Guo L, Liao S.

Mol Med Rep. 2018 Jan;17(1):172-178. doi: 10.3892/mmr.2017.7874. Epub 2017 Oct 25.

PubMed [citation]
PMID:
29115496
PMCID:
PMC5780116
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003513183.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 298 of the MITF protein (p.Ser298Pro). This variant is present in population databases (rs104893747, gnomAD 0.007%). This missense change has been observed in individual(s) with cutaneous melanoma and/or Waardenburg syndrome, type 2 (PMID: 8589691, 29115496, 29625052, 36451132). ClinVar contains an entry for this variant (Variation ID: 14277). 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 not expected to disrupt MITF protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MITF function (PMID: 10587587, 23787126). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 30, 2024