NM_001354604.2(MITF):c.1516G>C (p.Gly506Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 25, 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:: RCV003094100.3

Allele description [Variation Report for NM_001354604.2(MITF):c.1516G>C (p.Gly506Arg)]

NM_001354604.2(MITF):c.1516G>C (p.Gly506Arg)

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.1516G>C (p.Gly506Arg)

HGVS:

NC_000003.12:g.69965183G>C
NG_011631.1:g.230702G>C
NM_000248.4:c.1195G>C
NM_001184967.2:c.1342G>C
NM_001354604.2:c.1516G>CMANE SELECT
NM_001354605.2:c.1513G>C
NM_001354606.2:c.1495G>C
NM_001354607.2:c.1447G>C
NM_001354608.2:c.1342G>C
NM_006722.3:c.1495G>C
NM_198158.3:c.1177G>C
NM_198159.3:c.1498G>C
NM_198177.3:c.1450G>C
NM_198178.3:c.1009G>C
NP_000239.1:p.Gly399Arg
NP_001171896.1:p.Gly448Arg
NP_001341533.1:p.Gly506Arg
NP_001341534.1:p.Gly505Arg
NP_001341535.1:p.Gly499Arg
NP_001341536.1:p.Gly483Arg
NP_001341537.1:p.Gly448Arg
NP_006713.1:p.Gly499Arg
NP_937801.1:p.Gly393Arg
NP_937802.1:p.Gly500Arg
NP_937820.1:p.Gly484Arg
NP_937821.2:p.Gly337Arg
LRG_776t1:c.1195G>C
LRG_776:g.230702G>C
NC_000003.11:g.70014334G>C
NM_000248.3:c.1195G>C

Protein change:

G337R

Links:

dbSNP: rs531830542

NCBI 1000 Genomes Browser:

rs531830542

Molecular consequence:

NM_000248.4:c.1195G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001184967.2:c.1342G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354604.2:c.1516G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354605.2:c.1513G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354606.2:c.1495G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354607.2:c.1447G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354608.2:c.1342G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006722.3:c.1495G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198158.3:c.1177G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198159.3:c.1498G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198177.3:c.1450G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198178.3:c.1009G>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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003453398	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26850479, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003453398

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2024)

germline

clinical testing

PubMed (2)
[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

A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes.

Tekin D, Yan D, Bademci G, Feng Y, Guo S, Foster J 2nd, Blanton S, Tekin M, Liu X.

Hear Res. 2016 Mar;333:179-184. doi: 10.1016/j.heares.2016.01.018. Epub 2016 Feb 2.

PubMed [citation]

PMID:: 26850479
PMCID:: PMC4798889

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, SCV003453398.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 399 of the MITF protein (p.Gly399Arg). This variant is present in population databases (rs531830542, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of Waardenburg Syndrome, type 2A (PMID: 26850479). ClinVar contains an entry for this variant (Variation ID: 1687701). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MITF protein function. 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: Oct 13, 2024

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