ClinVar Genomic variation as it relates to human health
NM_000372.5(TYR):c.1118C>A (p.Thr373Lys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000372.5(TYR):c.1118C>A (p.Thr373Lys)
Variation ID: 3774 Accession: VCV000003774.58
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q14.3 11: 89227904 (GRCh38) [ NCBI UCSC ] 11: 88961072 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 20, 2014 Apr 20, 2024 Apr 16, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000372.5:c.1118C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000363.1:p.Thr373Lys missense NC_000011.10:g.89227904C>A NC_000011.9:g.88961072C>A NG_008748.1:g.55033C>A P14679:p.Thr373Lys - Protein change
- T373K
- Other names
- T355K
- Canonical SPDI
- NC_000011.10:89227903:C:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00034
Trans-Omics for Precision Medicine (TOPMed) 0.00047
The Genome Aggregation Database (gnomAD) 0.00051
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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TYR | - | - |
GRCh38 GRCh37 |
656 | 677 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Apr 16, 2024 | RCV000003973.31 | |
Pathogenic (8) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000085898.38 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 15, 2020 | RCV000335429.14 | |
Pathogenic (2) |
criteria provided, single submitter
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Oct 25, 2023 | RCV001542596.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 11, 2022 | RCV002476920.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 10, 2022 | RCV003150806.8 | |
Pathogenic (1) |
criteria provided, single submitter
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Jul 28, 2023 | RCV003387500.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 14, 2023 | RCV003390638.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jun 25, 2015)
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criteria provided, single submitter
Method: clinical testing
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Albinism, oculocutaneous, type IA
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000249332.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Oculocutaneous albinism
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000374874.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The TYR c.1118C>A (p.Thr373Lys) missense variant has been reported in seven studies in which it is found in a total of 35 patients with oculocutaneous … (more)
The TYR c.1118C>A (p.Thr373Lys) missense variant has been reported in seven studies in which it is found in a total of 35 patients with oculocutaneous albinism, including in one in a homozygous state, in 29 in a compound heterozygous state (including one sibling pair and three sisters), and in five in a heterozygous state. None of the affected individuals demonstrated detectable tyrosinase activity, with carriers having low activity compared to controls (Spritz et al. 1990; Oetting et al. 1991; Tripathi et al. 1992; Park et al. 1993; Oetting et al. 1993; Hutton et al. 2008; Gargiulo et al. 2011). Segregation of the p.Thr373Lys variant with disease was shown in several of the studies (Spritz RA et al. 1990; Park et al. 1993; Gargiulo et al. 2011). The p.Thr373Lys variant was absent from 26 control alleles but is reported at a frequency of 0.00081 in the European American population of the Exome Sequencing Project. The Thr373 residue is conserved and located in the region of the protein involved in binding copper which is necessary for catalytic activity (Tripathi et al. 1992). Park et al. (1993) showed that the variant protein was not processed to the mature glycosylated form. Immunohistochemistry studies in COS7 cells by Toyofuku et al. (2001) showed that the p.Thr373Lys variant protein is retained in the ER, in contrast to the wild type protein. Transient expression studies in transfected HeLa cells demonstrated that the p.Thr373Lys variant abolished all three catalytic activities associated with the wild type tyrosinase and was unable to produce melanin (Tripathi et al. 1992). Based on the collective evidence, the p.Thr373Lys variant is classified as pathogenic for oculocutaneous albinism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Oct 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV003839048.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
This TYR variant (rs61754388) is rare (<0.1%) in a large population dataset (gnomAD: 100/282382 total alleles; 0.035%; no homozygotes) and has been reported in ClinVar. … (more)
This TYR variant (rs61754388) is rare (<0.1%) in a large population dataset (gnomAD: 100/282382 total alleles; 0.035%; no homozygotes) and has been reported in ClinVar. It is one of the most commonly reported TYR variants in individuals of European ancestry with OCA1. This variant has been observed in a homozygous or compound heterozygous state with another pathogenic TYR variant and has been shown to segregate with disease in affected families. This amino acid substitution (p.Thr373Lys) disrupts a signal for N-glycosylation, which results in incomplete processing of the tyrosinase enzyme to its mature glycosylated form and retention of the protein in the endoplasmic reticulum (ER). Experimental studies in transfected HeLa cells demonstrate that the p.Thr373Lys variant abolishes catalytic activity. We consider c.1118C>A to be pathogenic. (less)
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Pathogenic
(Oct 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Oculocutaneous albinism type 1B
Affected status: unknown
Allele origin:
germline
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Johns Hopkins Genomics, Johns Hopkins University
Accession: SCV003839049.1
First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
This TYR variant (rs61754388) is rare (<0.1%) in a large population dataset (gnomAD: 100/282382 total alleles; 0.035%; no homozygotes) and has been reported in ClinVar. … (more)
This TYR variant (rs61754388) is rare (<0.1%) in a large population dataset (gnomAD: 100/282382 total alleles; 0.035%; no homozygotes) and has been reported in ClinVar. It is one of the most commonly reported TYR variants in individuals of European ancestry with OCA1. This variant has been observed in a homozygous or compound heterozygous state with another pathogenic TYR variant and has been shown to segregate with disease in affected families. This amino acid substitution (p.Thr373Lys) disrupts a signal for N-glycosylation, which results in incomplete processing of the tyrosinase enzyme to its mature glycosylated form and retention of the protein in the endoplasmic reticulum (ER). Experimental studies in transfected HeLa cells demonstrate that the p.Thr373Lys variant abolishes catalytic activity. We consider c.1118C>A to be pathogenic. (less)
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Pathogenic
(Aug 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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TYR-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004109927.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The TYR c.1118C>A variant is predicted to result in the amino acid substitution p.Thr373Lys. This variant has been reported as causative for oculocutaneous albinism when … (more)
The TYR c.1118C>A variant is predicted to result in the amino acid substitution p.Thr373Lys. This variant has been reported as causative for oculocutaneous albinism when present with a second pathogenic variant (Opitz et al. 2004. PubMed ID: 15146472; King et al. 2003. PubMed ID: 13680365, Table 2; Hutton & Spritz. 2008. PubMed ID: 18463683, Table 1). This variant is reported in 0.068% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-88961072-C-A). This variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/3774/). Given all the evidence, we interpret c.1118C>A (p.Thr373Lys) as pathogenic. (less)
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Pathogenic
(Jan 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001248574.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Comment:
TYR: PM3:Very Strong, PM2, PP4, PS3:Supporting
Number of individuals with the variant: 7
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Pathogenic
(Jan 15, 2020)
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criteria provided, single submitter
Method: clinical testing
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Oculocutaneous albinism
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Study: CSER-MedSeq
Accession: SCV000245677.2 First in ClinVar: Sep 14, 2015 Last updated: Apr 20, 2024 |
Comment:
The Thr373Lys variant in TYR has been reported in >40 individuals with Oculocutaneous albinism and was found to segregate with disease in 3 affected relatives … (more)
The Thr373Lys variant in TYR has been reported in >40 individuals with Oculocutaneous albinism and was found to segregate with disease in 3 affected relatives from 1 family (Spritz 1990, Gershoni-Baruch 1994, King 2003, Opitz 2004, Hutton 2008, Hutton 2008, Cargiulo 2011). It has also been identified in 0.07% (88/128890) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID: 3774). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In vitro functional studies suggest this variant leads to abolished TYR activity (Tripathi 1992). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Oculocutaneous albinism. ACMG/AMP Criteria applied: PM3_Very Strong, PP1_Strong, PS3_Moderate. (less)
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Pathogenic
(Mar 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000228863.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 6
Sex: mixed
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Pathogenic
(Jul 22, 2021)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001821962.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Sex: mixed
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Pathogenic
(Jul 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581133.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PS3, PM3, PP1_MOD, PM2_SUP, PP3
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Number of individuals with the variant: 2
Sex: female
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Pathogenic
(Nov 05, 2021)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556367.2
First in ClinVar: Aug 08, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768421.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with oculocutaneous albinism type IA (MIM#203100) and type IB (MIM#606952). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to lysine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (100 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (p.(Thr373Ala):1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated tyrosinase domain (NCBI). (I) 0801 - This variant has very strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with albinism or ocular albinism (ClinVar, PMIDs: 2342539, 18326704, 29345414). (SP) 0901 - This variant has strong evidence for segregation with disease. This variant has been identified in a family with at least four affected individuals (PMID: 2342539). (SP) 1205 - This variant has been shown to be maternally inherited (by segregation analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Pathogenic
(Jan 11, 2022)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN Oculocutaneous albinism type 1B
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000611335.2
First in ClinVar: Nov 11, 2017 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000329959.7
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect, specifically, T373K transfected cells had no tyrosine hydroxylase activity, undetectable melanin production, and showed the T373K mutant protein … (more)
Published functional studies demonstrate a damaging effect, specifically, T373K transfected cells had no tyrosine hydroxylase activity, undetectable melanin production, and showed the T373K mutant protein was unable to leave the endoplasmic reticulum (Tripathi et al., 1992; Toyofuku et al., 2001). A separate in vitro study also suggests improper folding of the T373K protein (Dolinska et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9242509, 11284711, 23085273, 2342539, 27775880, 28484254, 1429711, 27535533, 18463683, 29036293, 28555837, 25533962, 31233279, 31719542, 28976636, 32543925, 31980526, 31589614, 33077847) (less)
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Pathogenic
(Jul 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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TYR-related disorder
Affected status: yes
Allele origin:
germline
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Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Accession: SCV004099263.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
PS3, PM3_Very Strong, PP3
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Pathogenic
(Oct 25, 2023)
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criteria provided, single submitter
Method: clinical testing
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SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004207545.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001580868.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 373 of the TYR protein (p.Thr373Lys). … (more)
This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 373 of the TYR protein (p.Thr373Lys). This variant is present in population databases (rs61754388, gnomAD 0.07%). This missense change has been observed in individuals with oculocutaneous albinism (PMID: 2342539, 9259202, 13680365, 18326704; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as Thr355Lys. ClinVar contains an entry for this variant (Variation ID: 3774). 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 not expected to disrupt TYR protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects TYR function (PMID: 1429711, 9242509, 27775880). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Apr 16, 2024)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004814164.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Clinical Features:
Albinism (present)
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Pathogenic
(Jul 15, 1992)
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no assertion criteria provided
Method: literature only
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ALBINISM, OCULOCUTANEOUS, TYPE IA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000024138.3
First in ClinVar: Apr 04, 2013 Last updated: Feb 06, 2020 |
Comment on evidence:
In a woman with classic albinism (OCA1A; 203100), Spritz et al. (1990) demonstrated compound heterozygosity for 2 allelic single-base missense substitutions in the tyrosinase gene … (more)
In a woman with classic albinism (OCA1A; 203100), Spritz et al. (1990) demonstrated compound heterozygosity for 2 allelic single-base missense substitutions in the tyrosinase gene that altered codons 355 (thr-to-lys) and 365 (asp-to-asn). These substitutions would be expected to cause a severe defect of tyrosinase activity. Both result in changes of net charge, and both occur in a region of predicted helical structure within the so-called copper-binding region of the enzyme. In another numbering system, this is referred to as THR373LYS (King et al., 1991). In a case of type IA oculocutaneous albinism, Oetting et al. (1991) identified a change from ACA to AAA in codon 373 resulting in substitution of lysine for threonine. Also see Tripathi et al. (1992). (less)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760288.1
First in ClinVar: Jul 28, 2021 Last updated: Jul 28, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001925021.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954491.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964975.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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not provided
(-)
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no classification provided
Method: not provided
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not provided
Affected status: not provided
Allele origin:
not provided
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Retina International
Accession: SCV000118041.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_TYR:c.1118C>A
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Molecular characterization of a series of 990 index patients with albinism. | Lasseaux E | Pigment cell & melanoma research | 2018 | PMID: 29345414 |
Oculocutaneous albinism type 1: link between mutations, tyrosinase conformational stability, and enzymatic activity. | Dolinska MB | Pigment cell & melanoma research | 2017 | PMID: 27775880 |
DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. | Simeonov DR | Human mutation | 2013 | PMID: 23504663 |
Mutational analysis of TYR gene and its structural consequences in OCA1A. | K B | Gene | 2013 | PMID: 23085273 |
Molecular and clinical characterization of albinism in a large cohort of Italian patients. | Gargiulo A | Investigative ophthalmology & visual science | 2011 | PMID: 20861488 |
Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. | Hutton SM | The Journal of investigative dermatology | 2008 | PMID: 18463683 |
A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients. | Hutton SM | Investigative ophthalmology & visual science | 2008 | PMID: 18326704 |
Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism. | Opitz S | Human mutation | 2004 | PMID: 15146472 |
Tyrosinase gene mutations in oculocutaneous albinism 1 (OCA1): definition of the phenotype. | King RA | Human genetics | 2003 | PMID: 13680365 |
The molecular basis of oculocutaneous albinism type 1 (OCA1): sorting failure and degradation of mutant tyrosinases results in a lack of pigmentation. | Toyofuku K | The Biochemical journal | 2001 | PMID: 11284711 |
Endoplasmic reticulum retention is a common defect associated with tyrosinase-negative albinism. | Halaban R | Proceedings of the National Academy of Sciences of the United States of America | 2000 | PMID: 10823941 |
Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1). | Spritz RA | Human mutation | 1997 | PMID: 9259202 |
Mutational analysis of copper binding by human tyrosinase. | Spritz RA | The Journal of investigative dermatology | 1997 | PMID: 9242509 |
Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel. | Gershoni-Baruch R | American journal of human genetics | 1994 | PMID: 8128955 |
A frequent tyrosinase gene mutation associated with type I-A (tyrosinase-negative) oculocutaneous albinism in Puerto Rico. | Oetting WS | American journal of human genetics | 1993 | PMID: 8434585 |
Molecular analyses of a tyrosinase-negative albino family. | Park KC | American journal of human genetics | 1993 | PMID: 8430701 |
Tyrosinase gene mutations in type I (tyrosinase-deficient) oculocutaneous albinism define two clusters of missense substitutions. | Tripathi RK | American journal of medical genetics | 1992 | PMID: 1642278 |
Mutational mapping of the catalytic activities of human tyrosinase. | Tripathi RK | The Journal of biological chemistry | 1992 | PMID: 1429711 |
Non-random distribution of missense mutations within the human tyrosinase gene in type I (tyrosinase-related) oculocutaneous albinism. | King RA | Molecular biology & medicine | 1991 | PMID: 1943686 |
Three different frameshift mutations of the tyrosinase gene in type IA oculocutaneous albinism. | Oetting WS | American journal of human genetics | 1991 | PMID: 1905879 |
Homozygous tyrosinase gene mutation in an American black with tyrosinase-negative (type IA) oculocutaneous albinism. | Spritz RA | American journal of human genetics | 1991 | PMID: 1899321 |
Detection of mutations in the tyrosinase gene in a patient with type IA oculocutaneous albinism. | Spritz RA | The New England journal of medicine | 1990 | PMID: 2342539 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TYR | - | - | - | - |
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Text-mined citations for rs61754388 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.