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

This record was updated by the submitter. Please see the current version.

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:: RCV003767914.1

Allele description

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

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iron-sulfur cluster transfer protein NUBPL isoform 1 precursor [Homo sapiens]
iron-sulfur cluster transfer protein NUBPL isoform 1 precursor [Homo sapiens]
gi|157384956|ref|NP_079428.2|

Protein
Abortion, Threatened
Abortion, Threatened
UTERINE BLEEDING from a GESTATION of less than 20 weeks without any CERVICAL DILATATION. It is characterized by vaginal bleeding, lower back discomfort, or midline pelvic cram...<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004580123	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33111345, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004580123

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 17, 2023)

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

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 Invitae, SCV004580123.1

#	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 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.

#	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: Mar 5, 2024

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