NM_000372.5(TYR):c.1205G>A (p.Arg402Gln) AND not provided

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

Germline classification:: Conflicting interpretations of pathogenicity; other (5 submissions)
Last evaluated:: Mar 1, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000085910.26

Allele description

NM_000372.5(TYR):c.1205G>A (p.Arg402Gln)

Gene:

TYR:tyrosinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.3

Genomic location:

Preferred name:

NM_000372.5(TYR):c.1205G>A (p.Arg402Gln)

Other names:

TYR, ARG402GLN (rs1126809)

HGVS:

NC_000011.10:g.89284793G>A
NG_008748.1:g.111922G>A
NM_000372.5:c.1205G>AMANE SELECT
NP_000363.1:p.Arg402Gln
NC_000011.9:g.89017961G>A
NM_000372.4:c.1205G>A
P14679:p.Arg402Gln

Protein change:

R402Q; ARG402GLN

Links:

UniProtKB: P14679#VAR_007686; OMIM: 606933.0009; dbSNP: rs1126809

NCBI 1000 Genomes Browser:

rs1126809

Molecular consequence:

NM_000372.5:c.1205G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Homo sapiens serine/threonine kinase 35 (STK35), transcript variant X...
PREDICTED: Homo sapiens serine/threonine kinase 35 (STK35), transcript variant X1, mRNA
gi|2217334540|ref|XM_011529174.4|

Nucleotide
Pathogen: environmental/food/other sample from Salmonella enterica subsp. enteri...
Pathogen: environmental/food/other sample from Salmonella enterica subsp. enterica serovar Saintpaul

biosample
txid33448[Organism:noexp] (480)
Protein
Genome annotation of the blackstripe livebearer Poeciliopsis prolifica, a placen...
Genome annotation of the blackstripe livebearer Poeciliopsis prolifica, a placental Poeciliid for understanding fish placenta evolution
Genome annotation of the blackstripe livebearer Poeciliopsis prolifica, a placental Poeciliid for understanding fish placenta evolution

BioProject
txid62324[orgn] AND "isolate TZMU34 0"[All Fields] (1)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118053	Retina International	no classification provided	not provided	not provided	not provided
SCV000340022	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Oct 24, 2017)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 1429711, 1820207, 18326704, 19208379, 19533789, 21541274, 23504663, 25216246, 7704033 Citation Link,
SCV000597779	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	other (May 24, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001731474	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002821657	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Mar 1, 2024)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	23	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	40	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
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational mapping of the catalytic activities of human tyrosinase.

Tripathi RK, Hearing VJ, Urabe K, Aroca P, Spritz RA.

J Biol Chem. 1992 Nov 25;267(33):23707-12.

PubMed [citation]

PMID:: 1429711

A polymorphism of the human tyrosinase gene is associated with temperature-sensitive enzymatic activity.

Tripathi RK, Giebel LB, Strunk KM, Spritz RA.

Gene Expr. 1991 May;1(2):103-10.

PubMed [citation]

PMID:: 1820207
PMCID:: PMC5952204

See all PubMed Citations (11)

Details of each submission

From Retina International, SCV000118053.1

#	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 Eurofins Ntd Llc (ga), SCV000340022.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	23	not provided	not provided	clinical testing	PubMed (9)

#	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		23	not provided	not provided	not provided

From Genetic Services Laboratory, University of Chicago, SCV000597779.3

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

Description

DNA sequence analysis of the TYR gene demonstrated a sequence change, c.1205G>A, in exon 4 that results in an amino acid change, p.Arg402Gln. The p.Arg402Gln substitution is a well-documented temperature-sensitive reduced function allele that alone is not sufficient to cause an oculocutaneous albinism phenotype. However, the p.Arg402Gln substitution, if found in compound heterozygous state with a pathogenic mutation, may be associated with a mild oculocutaneous albinism type 1B (OCA1B) or ocular albinism (OA) phenotype (PMIDs: 7704033, 19938076, 18463683, 18326704, 23504663). The p.Arg402Gln substitution has been described in the gnomAD database with a high population frequency of 28% in the European American population (dbSNP rs1126809). Some studies have suggested that the p.Arg402Gln substitution is not associated with mild OCA1B or OA phenotype, due to its high frequency in the general population and the presence of this variant in trans with a pathogenic variant in unaffected parents (PMID: 19208379). It has been proposed that the p.Arg402Gln variant causes a partial albinism phenotype only when paired with certain genetic backgrounds (PMIDs: 7704033, 19938076) and multiple studies have shown that the p.Arg402Gln variant is more common in OCA patients with one TYR pathogenic variant than in patients with two pathogenic variants (PMIDs: 18463683, 18326704, 19938076, 23504663).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001731474.4

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

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV002821657.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	40	not provided	not provided	clinical testing	not provided

Description

TYR: PM3:Very Strong, PM2, PM5, PP4, BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		40	not provided	not provided	not provided

Last Updated: May 1, 2024

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