ClinVar Genomic variation as it relates to human health
NM_000372.5(TYR):c.1064C>T (p.Ala355Val)
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.
Pathogenic(4); Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000372.5(TYR):c.1064C>T (p.Ala355Val)
Variation ID: 212520 Accession: VCV000212520.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q14.3 11: 89227850 (GRCh38) [ NCBI UCSC ] 11: 88961018 (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 Oct 5, 2015 Feb 14, 2024 Dec 13, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000372.5:c.1064C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000363.1:p.Ala355Val missense NC_000011.10:g.89227850C>T NC_000011.9:g.88961018C>T NG_008748.1:g.54979C>T P14679:p.Ala355Val - Protein change
- A355V
- Other names
- -
- Canonical SPDI
- NC_000011.10:89227849:C:T
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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
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00003
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Trans-Omics for Precision Medicine (TOPMed) 0.00021
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
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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 |
657 | 678 |
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jul 22, 2021 | RCV000195157.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV000778350.5 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 13, 2023 | RCV001853121.6 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 5, 2023 | RCV003462302.1 |
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
(Apr 17, 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: SCV000249331.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Uncertain significance
(Apr 28, 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: SCV000914550.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The TYR c.1064C>T (p.Ala355Val) variant is a missense variant that has been reported in one study, where it was found in a compound heterozygous state … (more)
The TYR c.1064C>T (p.Ala355Val) variant is a missense variant that has been reported in one study, where it was found in a compound heterozygous state in one individual with oculocutaneous albinism (Simeonov et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00036 in the South Asian population of the Exome Aggregation Consortium. The evidence for this variant is limited. The p.Ala355Val variant is therefore classified as a variant of uncertain significance but suspicious for pathogenicity 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
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138403.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Likely 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: SCV001821907.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Sex: mixed
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Pathogenic
(Oct 05, 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: SCV004207562.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Dec 13, 2023)
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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: SCV002242197.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 355 of the TYR protein (p.Ala355Val). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 355 of the TYR protein (p.Ala355Val). This variant is present in population databases (rs151206295, gnomAD 0.03%). This missense change has been observed in individuals with oculocutaneous albinism type 1A (PMID: 23504663, 27734839, 27959697). ClinVar contains an entry for this variant (Variation ID: 212520). 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%. This variant disrupts the p.Ala355 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9259202, 10987646, 15146472). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 12, 2014)
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no assertion criteria provided
Method: clinical testing
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Tyrosinase-negative oculocutaneous albinism
(Autosomal recessive inheritance)
Affected status: unknown, yes
Allele origin:
maternal,
germline
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Baylor Genetics
Accession: SCV000328777.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
Comment:
This pathogenic variant has been previously described [PMID:9259202,23504663] and was found in trans with another pathogenic variant in TYR (NM_000372.4, c.229C>T) in an individual with … (more)
This pathogenic variant has been previously described [PMID:9259202,23504663] and was found in trans with another pathogenic variant in TYR (NM_000372.4, c.229C>T) in an individual with autism, regression in language skills at 14mo of age, macrocephaly, joint laxity, atlantoaxial instability, fractures, delayed bone age, short stature, hip dysplasia, tyrosinase-negative oculocutaneous and cutaneous albinism and decrease pain sensitivity. A likely pathogenic de novo variant in TGFB2 (NM_003238.3, c.458G>A) was reported in the same individual. Heterozygotes for this variant are expected to be asymptomatic carriers. (less)
Observation 1:
Number of individuals with the variant: 1
Family history: yes
Age: 0-9 years
Sex: male
Ethnicity/Population group: Caucasians
Observation 2:
Number of individuals with the variant: 1
Age: 0-9 years
Sex: male
Ethnicity/Population group: South East Asian
Geographic origin: India
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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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Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. | Posey JE | The New England journal of medicine | 2017 | PMID: 27959697 |
Clinical evaluation and molecular screening of a large consecutive series of albino patients. | Mauri L | Journal of human genetics | 2017 | PMID: 27734839 |
DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. | Simeonov DR | Human mutation | 2013 | PMID: 23504663 |
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 |
Novel and recurrent mutations in the tyrosinase gene and the P gene in the German albino population. | Passmore LA | Human genetics | 1999 | PMID: 10987646 |
Novel mutations of the tyrosinase (TYR) gene in type I oculocutaneous albinism (OCA1). | Spritz RA | Human mutation | 1997 | PMID: 9259202 |
Text-mined citations for rs151206295 ...
HelpRecord last updated Jun 10, 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.