NM_000372.5(TYR):c.290G>T (p.Gly97Val) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001969826.7

Allele description [Variation Report for NM_000372.5(TYR):c.290G>T (p.Gly97Val)]

NM_000372.5(TYR):c.290G>T (p.Gly97Val)

Gene:

TYR:tyrosinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q14.3

Genomic location:

Preferred name:

NM_000372.5(TYR):c.290G>T (p.Gly97Val)

HGVS:

NC_000011.10:g.89178243G>T
NG_008748.1:g.5372G>T
NM_000372.5:c.290G>TMANE SELECT
NP_000363.1:p.Gly97Val
NC_000011.9:g.88911411G>T
NM_000372.4:c.290G>T

Protein change:

G97V

Links:

dbSNP: rs1320376090

NCBI 1000 Genomes Browser:

rs1320376090

Molecular consequence:

NM_000372.5:c.290G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002219801	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 15, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15381243, 27734839, 27537549, 28492532
SCV002820517	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jul 12, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002219801

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 15, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002820517

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jul 12, 2022)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Tyrosinase gene analysis in Japanese patients with oculocutaneous albinism.

Goto M, Sato-Matsumura KC, Sawamura D, Yokota K, Nakamura H, Shimizu H.

J Dermatol Sci. 2004 Sep;35(3):215-20.

PubMed [citation]

PMID:: 15381243

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002219801.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

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. This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 97 of the TYR protein (p.Gly97Val). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with ocular albinism (PMID: 15381243, 27734839). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1442280). Experimental studies have shown that this missense change affects TYR function (PMID: 27537549). 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

From GeneDx, SCV002820517.1

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

Description

Published functional studies demonstrate a damaging effect with absent enzyme activity (Mondal et al., 2016); Observed with a second variant in an individual with OCA in the literature, and testing of one parent suggests the variants are likely present on opposite alleles (in trans) (Goto et al., 2004); Not observed at significant frequency in large population cohorts (gnomAD); 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: 27537549, 15381243)

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine