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NM_001354604.2(MITF):c.1129C>T (p.Arg377Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 14, 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:
RCV005222836.1

Allele description [Variation Report for NM_001354604.2(MITF):c.1129C>T (p.Arg377Ter)]

NM_001354604.2(MITF):c.1129C>T (p.Arg377Ter)

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.1129C>T (p.Arg377Ter)
HGVS:
  • NC_000003.12:g.69959370C>T
  • NG_011631.1:g.224889C>T
  • NM_000248.4:c.808C>T
  • NM_001184967.2:c.955C>T
  • NM_001354604.2:c.1129C>TMANE SELECT
  • NM_001354605.2:c.1126C>T
  • NM_001354606.2:c.1108C>T
  • NM_001354607.2:c.1060C>T
  • NM_001354608.2:c.955C>T
  • NM_006722.3:c.1108C>T
  • NM_198158.3:c.790C>T
  • NM_198159.3:c.1111C>T
  • NM_198177.3:c.1063C>T
  • NM_198178.3:c.622C>T
  • NP_000239.1:p.Arg270Ter
  • NP_001171896.1:p.Arg319Ter
  • NP_001341533.1:p.Arg377Ter
  • NP_001341534.1:p.Arg376Ter
  • NP_001341535.1:p.Arg370Ter
  • NP_001341536.1:p.Arg354Ter
  • NP_001341537.1:p.Arg319Ter
  • NP_006713.1:p.Arg370Ter
  • NP_937801.1:p.Arg264Ter
  • NP_937802.1:p.Arg371Ter
  • NP_937820.1:p.Arg355Ter
  • NP_937821.2:p.Arg208Ter
  • LRG_776t1:c.808C>T
  • LRG_776:g.224889C>T
  • NC_000003.11:g.70008521C>T
  • NM_000248.3:c.808C>T
  • NM_198159.2:c.1111C>T
  • p.Arg371X
Protein change:
R208*
Links:
dbSNP: rs876657699
NCBI 1000 Genomes Browser:
rs876657699
Molecular consequence:
  • NM_000248.4:c.808C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001184967.2:c.955C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354604.2:c.1129C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354605.2:c.1126C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354606.2:c.1108C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354607.2:c.1060C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001354608.2:c.955C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006722.3:c.1108C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198158.3:c.790C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198159.3:c.1111C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198177.3:c.1063C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_198178.3:c.622C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005863462Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 14, 2024) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A.

Nobukuni Y, Watanabe A, Takeda K, Skarka H, Tachibana M.

Am J Hum Genet. 1996 Jul;59(1):76-83.

PubMed [citation]
PMID:
8659547
PMCID:
PMC1915102

Review and update of mutations causing Waardenburg syndrome.

Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N.

Hum Mutat. 2010 Apr;31(4):391-406. doi: 10.1002/humu.21211. Review.

PubMed [citation]
PMID:
20127975
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV005863462.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg270*) in the MITF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MITF are known to be pathogenic (PMID: 8659547, 20127975). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Waardenburg syndrome (PMID: 27759048, 34142234). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 228363). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 16, 2025