NM_000372.5(TYR):c.649del (p.Arg217fs) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 30, 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:: RCV000085963.5

Allele description [Variation Report for NM_000372.5(TYR):c.649del (p.Arg217fs)]

NM_000372.5(TYR):c.649del (p.Arg217fs)

Gene:

TYR:tyrosinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q14.3

Genomic location:

Preferred name:

NM_000372.5(TYR):c.649del (p.Arg217fs)

HGVS:

NC_000011.10:g.89178602del
NG_008748.1:g.5731del
NM_000372.5:c.649delMANE SELECT
NP_000363.1:p.Arg217fs
NC_000011.9:g.88911770del
NM_000372.4:c.649del
NM_000372.4:c.649delC

Protein change:

R217fs

Links:

dbSNP: rs61754364

NCBI 1000 Genomes Browser:

rs61754364

Molecular consequence:

NM_000372.5:c.649del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118106	Retina International	no classification provided	not provided	not provided	not provided
SCV003441024	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23504663, 8128955, 28492532
SCV005325010	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 19, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118106

Retina International

no classification provided

not provided

SCV003441024

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 2023)

germline

clinical testing

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

SCV005325010

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 19, 2023)

germline

clinical testing

Citation Link

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_TYR:c.649delC: SCV000118106

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics.

Simeonov DR, Wang X, Wang C, Sergeev Y, Dolinska M, Bower M, Fischer R, Winer D, Dubrovsky G, Balog JZ, Huizing M, Hart R, Zein WM, Gahl WA, Brooks BP, Adams DR.

Hum Mutat. 2013 Jun;34(6):827-35. doi: 10.1002/humu.22315. Epub 2013 Apr 30. Review.

PubMed [citation]

PMID:: 23504663
PMCID:: PMC3959784

Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel.

Gershoni-Baruch R, Rosenmann A, Droetto S, Holmes S, Tripathi RK, Spritz RA.

Am J Hum Genet. 1994 Apr;54(4):586-94.

PubMed [citation]

PMID:: 8128955
PMCID:: PMC1918101

See all PubMed Citations (3)

Details of each submission

From Retina International, SCV000118106.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003441024.2

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

Description

This sequence change creates a premature translational stop signal (p.Arg217Glyfs*9) in the TYR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYR are known to be pathogenic (PMID: 23504663). This variant is present in population databases (rs61754364, gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with oculocutaneous albinism (PMID: 8128955). This variant is also known as R217ùùôC. ClinVar contains an entry for this variant (Variation ID: 99574). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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, SCV005325010.1

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

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 8128955)

#	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: Oct 8, 2024

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