NM_000372.5(TYR):c.816G>C (p.Trp272Cys) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 7, 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:: RCV000085971.3

Allele description [Variation Report for NM_000372.5(TYR):c.816G>C (p.Trp272Cys)]

NM_000372.5(TYR):c.816G>C (p.Trp272Cys)

Gene:

TYR:tyrosinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.3

Genomic location:

Preferred name:

NM_000372.5(TYR):c.816G>C (p.Trp272Cys)

HGVS:

NC_000011.10:g.89178769G>C
NG_008748.1:g.5898G>C
NM_000372.5:c.816G>CMANE SELECT
NP_000363.1:p.Trp272Cys
NC_000011.9:g.88911937G>C
NM_000372.4:c.816G>C
P14679:p.Trp272Cys

Protein change:

W272C

Links:

UniProtKB: P14679#VAR_021705; dbSNP: rs62645902

NCBI 1000 Genomes Browser:

rs62645902

Molecular consequence:

NM_000372.5:c.816G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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nsv1001715 (0)
PopSet
nsv1001715 AND 1[s_discriminator] (0)
dbGaP
SRX13456633 (1)
SRA
Homo sapiens immediate early response 3, mRNA (cDNA clone MGC:13037 IMAGE:361708...
Homo sapiens immediate early response 3, mRNA (cDNA clone MGC:13037 IMAGE:3617088), complete cds
gi|13477228|gb|BC005080.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118114	Retina International	no classification provided	not provided	not provided	not provided
SCV004296109	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 7, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10987646, 15606524, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118114

Retina International

no classification provided

not provided

SCV004296109

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 7, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_TYR:c.816G>C: SCV000118114

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population.

Passmore LA, Kaesmann-Kellner B, Weber BH.

Hum Genet. 1999 Sep;105(3):200-10.

PubMed [citation]

PMID:: 10987646

Coinheritance of two rare genodermatoses (Papillon-Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study.

Hewitt C, Wu CL, Hattab FN, Amin W, Ghaffar KA, Toomes C, Sloan P, Read AP, James JA, Thakker NS.

Br J Dermatol. 2004 Dec;151(6):1261-5.

PubMed [citation]

PMID:: 15606524

See all PubMed Citations (3)

Details of each submission

From Retina International, SCV000118114.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296109.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 272 of the TYR protein (p.Trp272Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 10987646, 15606524). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99581). 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 TYR protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as 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: Sep 29, 2024

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