NM_001354604.2(MITF):c.1192C>G (p.Gln398Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 2023
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:: RCV003804407.2

Allele description [Variation Report for NM_001354604.2(MITF):c.1192C>G (p.Gln398Glu)]

NM_001354604.2(MITF):c.1192C>G (p.Gln398Glu)

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.1192C>G (p.Gln398Glu)

HGVS:

NC_000003.12:g.69964859C>G
NG_011631.1:g.230378C>G
NM_000248.4:c.871C>G
NM_001184967.2:c.1018C>G
NM_001354604.2:c.1192C>GMANE SELECT
NM_001354605.2:c.1189C>G
NM_001354606.2:c.1171C>G
NM_001354607.2:c.1123C>G
NM_001354608.2:c.1018C>G
NM_006722.3:c.1171C>G
NM_198158.3:c.853C>G
NM_198159.3:c.1174C>G
NM_198177.3:c.1126C>G
NM_198178.3:c.685C>G
NP_000239.1:p.Gln291Glu
NP_000239.1:p.Gln291Glu
NP_001171896.1:p.Gln340Glu
NP_001341533.1:p.Gln398Glu
NP_001341534.1:p.Gln397Glu
NP_001341535.1:p.Gln391Glu
NP_001341536.1:p.Gln375Glu
NP_001341537.1:p.Gln340Glu
NP_006713.1:p.Gln391Glu
NP_937801.1:p.Gln285Glu
NP_937802.1:p.Gln392Glu
NP_937820.1:p.Gln376Glu
NP_937821.2:p.Gln229Glu
LRG_776t1:c.871C>G
LRG_776:g.230378C>G
LRG_776p1:p.Gln291Glu
NC_000003.11:g.70014010C>G
NM_000248.3:c.871C>G

Protein change:

Q229E

Molecular consequence:

NM_000248.4:c.871C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.1018C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.1192C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.1189C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.1171C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.1123C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.1018C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.1171C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.853C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.1174C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.1126C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.685C>G - 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
SCV004596048	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 2023)	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

SCV004596048

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 2023)

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, SCV004596048.1

#	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 glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 291 of the MITF protein (p.Gln291Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MITF-related conditions. 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%. 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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