U.S. flag

An official website of the United States government

NM_001354604.2(MITF):c.953T>C (p.Leu318Pro) AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 17, 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:
RCV003767914.2

Allele description [Variation Report for NM_001354604.2(MITF):c.953T>C (p.Leu318Pro)]

NM_001354604.2(MITF):c.953T>C (p.Leu318Pro)

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.953T>C (p.Leu318Pro)
HGVS:
  • NC_000003.12:g.69951884T>C
  • NG_011631.1:g.217403T>C
  • NM_000248.4:c.632T>C
  • NM_001184967.2:c.779T>C
  • NM_001354604.2:c.953T>CMANE SELECT
  • NM_001354605.2:c.950T>C
  • NM_001354606.2:c.932T>C
  • NM_001354607.2:c.884T>C
  • NM_001354608.2:c.779T>C
  • NM_006722.3:c.932T>C
  • NM_198158.3:c.614T>C
  • NM_198159.3:c.935T>C
  • NM_198177.3:c.887T>C
  • NM_198178.3:c.446T>C
  • NP_000239.1:p.Leu211Pro
  • NP_000239.1:p.Leu211Pro
  • NP_001171896.1:p.Leu260Pro
  • NP_001341533.1:p.Leu318Pro
  • NP_001341534.1:p.Leu317Pro
  • NP_001341535.1:p.Leu311Pro
  • NP_001341536.1:p.Leu295Pro
  • NP_001341537.1:p.Leu260Pro
  • NP_006713.1:p.Leu311Pro
  • NP_937801.1:p.Leu205Pro
  • NP_937802.1:p.Leu312Pro
  • NP_937820.1:p.Leu296Pro
  • NP_937821.2:p.Leu149Pro
  • LRG_776t1:c.632T>C
  • LRG_776:g.217403T>C
  • LRG_776p1:p.Leu211Pro
  • NC_000003.11:g.70001035T>C
  • NM_000248.3:c.632T>C
  • NM_001354607.1:c.884T>C
Protein change:
L149P
Links:
dbSNP: rs1553704097
NCBI 1000 Genomes Browser:
rs1553704097
Molecular consequence:
  • NM_000248.4:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001184967.2:c.779T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354604.2:c.953T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354605.2:c.950T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354606.2:c.932T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354607.2:c.884T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354608.2:c.779T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006722.3:c.932T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198158.3:c.614T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198159.3:c.935T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198177.3:c.887T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_198178.3:c.446T>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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004580123Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 17, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1.

Brownstein Z, Gulsuner S, Walsh T, Martins FTA, Taiber S, Isakov O, Lee MK, Bordeynik-Cohen M, Birkan M, Chang W, Casadei S, Danial-Farran N, Abu-Rayyan A, Carlson R, Kamal L, Arnthórsson AÖ, Sokolov M, Gilony D, Lipschitz N, Frydman M, Davidov B, Macarov M, et al.

Clin Genet. 2020 Oct;98(4):353-364. doi: 10.1111/cge.13817. Epub 2020 Aug 24.

PubMed [citation]
PMID:
33111345
PMCID:
PMC8045518

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, SCV004580123.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 211 of the MITF protein (p.Leu211Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of Waardenburg syndrome (PMID: 33111345; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.935T>C (p.Leu312Pro). ClinVar contains an entry for this variant (Variation ID: 547531). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024