NM_000372.5(TYR):c.626C>T (p.Pro209Leu) AND Oculocutaneous albinism

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 8, 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:: RCV004579584.2

Allele description [Variation Report for NM_000372.5(TYR):c.626C>T (p.Pro209Leu)]

NM_000372.5(TYR):c.626C>T (p.Pro209Leu)

Gene:

TYR:tyrosinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.3

Genomic location:

Preferred name:

NM_000372.5(TYR):c.626C>T (p.Pro209Leu)

HGVS:

NC_000011.10:g.89178579C>T
NG_008748.1:g.5708C>T
NM_000372.5:c.626C>TMANE SELECT
NP_000363.1:p.Pro209Leu
NC_000011.9:g.88911747C>T

Protein change:

P209L

Links:

dbSNP: rs746581409

NCBI 1000 Genomes Browser:

rs746581409

Molecular consequence:

NM_000372.5:c.626C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Oculocutaneous albinism
Identifiers:: MONDO: MONDO:0018910; MedGen: C0078918; OMIM: PS203100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005062106	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Mar 8, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27734839, 18463683, 25216246 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005062106

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Mar 8, 2024)

germline

clinical testing

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

Citation Link

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

Clinical evaluation and molecular screening of a large consecutive series of albino patients.

Mauri L, Manfredini E, Del Longo A, Veniani E, Scarcello M, Terrana R, Radaelli AE, Calò D, Mingoia G, Rossetti A, Marsico G, Mazza M, Gesu GP, Cristina Patrosso M, Penco S, Piozzi E, Primignani P.

J Hum Genet. 2017 Feb;62(2):277-290. doi: 10.1038/jhg.2016.123. Epub 2016 Oct 13.

PubMed [citation]

PMID:: 27734839

Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

Hutton SM, Spritz RA.

J Invest Dermatol. 2008 Oct;128(10):2442-50. doi: 10.1038/jid.2008.109. Epub 2008 May 8.

PubMed [citation]

PMID:: 18463683
PMCID:: PMC3515683

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005062106.2

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

Description

Variant summary: TYR c.626C>T (p.Pro209Leu) results in a non-conservative amino acid change located in the Tyrosinase copper-binding domain (IPR002227) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251364 control chromosomes. c.626C>T has been reported in the literature as a homozygous or compound heterozygous genotype in at-least three individuals affected with Oculocutaneous Albinism. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25216246, 18463683, 27734839). ClinVar contains an entry for this variant (Variation ID: 1455534). Based on the evidence outlined above, the variant was 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: Nov 10, 2024

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