NM_001354604.2(MITF):c.937A>C (p.Lys313Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 21, 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:: RCV003781007.2

Allele description [Variation Report for NM_001354604.2(MITF):c.937A>C (p.Lys313Gln)]

NM_001354604.2(MITF):c.937A>C (p.Lys313Gln)

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.937A>C (p.Lys313Gln)

HGVS:

NC_000003.12:g.69951868A>C
NG_011631.1:g.217387A>C
NM_000248.4:c.616A>C
NM_001184967.2:c.763A>C
NM_001354604.2:c.937A>CMANE SELECT
NM_001354605.2:c.934A>C
NM_001354606.2:c.916A>C
NM_001354607.2:c.868A>C
NM_001354608.2:c.763A>C
NM_006722.3:c.916A>C
NM_198158.3:c.598A>C
NM_198159.3:c.919A>C
NM_198177.3:c.871A>C
NM_198178.3:c.430A>C
NP_000239.1:p.Lys206Gln
NP_000239.1:p.Lys206Gln
NP_001171896.1:p.Lys255Gln
NP_001341533.1:p.Lys313Gln
NP_001341534.1:p.Lys312Gln
NP_001341535.1:p.Lys306Gln
NP_001341536.1:p.Lys290Gln
NP_001341537.1:p.Lys255Gln
NP_006713.1:p.Lys306Gln
NP_937801.1:p.Lys200Gln
NP_937802.1:p.Lys307Gln
NP_937820.1:p.Lys291Gln
NP_937821.2:p.Lys144Gln
LRG_776t1:c.616A>C
LRG_776:g.217387A>C
LRG_776p1:p.Lys206Gln
NC_000003.11:g.70001019A>C
NM_000248.3:c.616A>C

Protein change:

K144Q

Molecular consequence:

NM_000248.4:c.616A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.763A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.937A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.934A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.916A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.868A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.763A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.916A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.598A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.919A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.871A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.430A>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

Recent activity

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LINC02787 long intergenic non-protein coding RNA 2787 [Homo sapiens]
LINC02787 long intergenic non-protein coding RNA 2787 [Homo sapiens]
Gene ID:105378852

Gene
LINC02787 AND (alive[prop]) (1)
Gene
uncharacterized protein LOC112096408 [Citrus x clementina]
uncharacterized protein LOC112096408 [Citrus x clementina]
gi|1350329895|ref|XP_024035600.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004569655	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 21, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22258527, 23787126, 27889061, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004569655

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 21, 2024)

germline

clinical testing

PubMed (4)
[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

Novel and recurrent non-truncating mutations of the MITF basic domain: genotypic and phenotypic variations in Waardenburg and Tietz syndromes.

Léger S, Balguerie X, Goldenberg A, Drouin-Garraud V, Cabot A, Amstutz-Montadert I, Young P, Joly P, Bodereau V, Holder-Espinasse M, Jamieson RV, Krause A, Chen H, Baumann C, Nunes L, Dollfus H, Goossens M, Pingault V.

Eur J Hum Genet. 2012 May;20(5):584-7. doi: 10.1038/ejhg.2011.234. Epub 2012 Jan 18.

PubMed [citation]

PMID:: 22258527
PMCID:: PMC3330215

MITF mutations associated with pigment deficiency syndromes and melanoma have different effects on protein function.

Grill C, Bergsteinsdóttir K, Ogmundsdóttir MH, Pogenberg V, Schepsky A, Wilmanns M, Pingault V, Steingrímsson E.

Hum Mol Genet. 2013 Nov 1;22(21):4357-67. doi: 10.1093/hmg/ddt285. Epub 2013 Jun 20.

PubMed [citation]

PMID:: 23787126
PMCID:: PMC3888191

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004569655.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 206 of the MITF protein (p.Lys206Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Waardenburg Syndrome (PMID: 22258527, 27889061). 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 expected to disrupt MITF protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects MITF function (PMID: 23787126, 27889061). 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.

#	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: Sep 29, 2024

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