NM_001354604.2(MITF):c.355-1062G>C AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 29, 2022
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:: RCV002534250.1

Allele description

NM_001354604.2(MITF):c.355-1062G>C

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.355-1062G>C

HGVS:

NC_000003.12:g.69936760G>C
NG_011631.1:g.202279G>C
NG_050802.1:g.2463G>C
NM_000248.4:c.33+5G>C
NM_001184967.2:c.199-1062G>C
NM_001184968.2:c.33+5G>C
NM_001354604.2:c.355-1062G>CMANE SELECT
NM_001354605.2:c.352-1062G>C
NM_001354606.2:c.352-1062G>C
NM_001354607.2:c.304-1062G>C
NM_001354608.2:c.199-1062G>C
NM_006722.3:c.352-1062G>C
NM_198158.3:c.33+5G>C
NM_198159.3:c.355-1062G>C
NM_198177.3:c.307-1062G>C
NM_198178.3:c.33+5G>C
LRG_776t1:c.33+5G>C
LRG_776:g.202279G>C
NC_000003.11:g.69985911G>C
NM_000248.3:c.33+5G>C

Links:

dbSNP: rs1236436555

NCBI 1000 Genomes Browser:

rs1236436555

Molecular consequence:

NM_000248.4:c.33+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001184967.2:c.199-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001184968.2:c.33+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354604.2:c.355-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354605.2:c.352-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354606.2:c.352-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354607.2:c.304-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001354608.2:c.199-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_006722.3:c.352-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198158.3:c.33+5G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198159.3:c.355-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198177.3:c.307-1062G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_198178.3:c.33+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Functional consequence:

effect on RNA splicing [Variation Ontology: 0362]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525336	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 29, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 21373256, 17576681, 9536098, 30117279, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525336

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 29, 2022)

germline

clinical testing

PubMed (5)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular Study of Three Lebanese and Syrian Patients with Waardenburg Syndrome and Report of Novel Mutations in the EDNRB and MITF Genes.

Haddad NM, Ente D, Chouery E, Jalkh N, Mehawej C, Khoueir Z, Pingault V, Mégarbané A.

Mol Syndromol. 2011 Jan;1(4):169-175. Epub 2011 Jan 10.

PubMed [citation]

PMID:: 21373256
PMCID:: PMC3042120

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003525336.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 1 of the MITF gene. It does not directly change the encoded amino acid sequence of the MITF protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (no rsID available, gnomAD no frequency). This variant has been observed in individuals with clinical features of autosomal dominant Waardenburg Syndrome, type 2A (PMID: 21373256, 30117279). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 545639). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 30117279). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 1, 2023

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