NM_001354604.2(MITF):c.1538G>A (p.Arg513Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 19, 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:: RCV002528269.3

Allele description [Variation Report for NM_001354604.2(MITF):c.1538G>A (p.Arg513Gln)]

NM_001354604.2(MITF):c.1538G>A (p.Arg513Gln)

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.1538G>A (p.Arg513Gln)

HGVS:

NC_000003.12:g.69965205G>A
NG_011631.1:g.230724G>A
NM_000248.4:c.1217G>A
NM_001184967.2:c.1364G>A
NM_001354604.2:c.1538G>AMANE SELECT
NM_001354605.2:c.1535G>A
NM_001354606.2:c.1517G>A
NM_001354607.2:c.1469G>A
NM_001354608.2:c.1364G>A
NM_006722.3:c.1517G>A
NM_198158.3:c.1199G>A
NM_198159.3:c.1520G>A
NM_198177.3:c.1472G>A
NM_198178.3:c.1031G>A
NP_000239.1:p.Arg406Gln
NP_000239.1:p.Arg406Gln
NP_001171896.1:p.Arg455Gln
NP_001341533.1:p.Arg513Gln
NP_001341534.1:p.Arg512Gln
NP_001341535.1:p.Arg506Gln
NP_001341536.1:p.Arg490Gln
NP_001341537.1:p.Arg455Gln
NP_006713.1:p.Arg506Gln
NP_937801.1:p.Arg400Gln
NP_937802.1:p.Arg507Gln
NP_937820.1:p.Arg491Gln
NP_937821.2:p.Arg344Gln
LRG_776t1:c.1217G>A
LRG_776:g.230724G>A
LRG_776p1:p.Arg406Gln
NC_000003.11:g.70014356G>A
NM_000248.3:c.1217G>A

Protein change:

R344Q

Links:

dbSNP: rs1018390529

NCBI 1000 Genomes Browser:

rs1018390529

Molecular consequence:

NM_000248.4:c.1217G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.1364G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.1538G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.1535G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.1517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.1469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.1364G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.1517G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.1199G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.1520G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.1472G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.1031G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002960313	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002960313

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002960313.2

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 406 of the MITF protein (p.Arg406Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MITF-related conditions. ClinVar contains an entry for this variant (Variation ID: 452346). 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%. 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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