Submissions for variant NM_000372.5(TYR):c.649C>T (p.Arg217Trp)

gnomAD frequency: 0.00029  dbSNP: rs63159160

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000085962	SCV000491313	pathogenic	not provided	2023-06-22	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 8477259, 1642278, 7963676, 13680365, 25216246, 28266639, 19626598, 18463683, 31589614, 34426522, 33800529, 31816670)
Fulgent Genetics, Fulgent Genetics	RCV000763290	SCV000893937	likely pathogenic	Tyrosinase-negative oculocutaneous albinism; Oculocutaneous albinism type 1B; Ocular albinism with congenital sensorineural hearing loss; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2018-10-31	criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV000003999	SCV001437671	pathogenic	Tyrosinase-negative oculocutaneous albinism	2019-06-20	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001332387	SCV001524704	uncertain significance	Oculocutaneous albinism type 1B	2019-04-11	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. These variants have been previously reported as disease-causing [PMID 1642278, 28266639, 1903591, 27775880, 25333069, 21906913, 28667292, 24123366, 9242509, 11284711, 1429711]
Genome-Nilou Lab	RCV000003999	SCV001821903	likely pathogenic	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
Invitae	RCV000085962	SCV002121290	pathogenic	not provided	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 217 of the TYR protein (p.Arg217Trp). This variant is present in population databases (rs63159160, gnomAD 0.04%). This missense change has been observed in individual(s) with ocular albinism (PMID: 1642278, 10987646, 27734839, 28266639). 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: 3795). 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%. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003460422	SCV004207563	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2023-10-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085962	SCV004700644	pathogenic	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TYR: PM3:Very Strong, PM2
OMIM	RCV000003999	SCV000024165	pathogenic	Tyrosinase-negative oculocutaneous albinism	1992-07-15	no assertion criteria provided	literature only
Retina International	RCV000085962	SCV000118105	not provided	not provided		no assertion provided	not provided
University of Washington Center for Mendelian Genomics, University of Washington	RCV000755070	SCV000882888	likely pathogenic	Nonsyndromic Oculocutaneous Albinism	2017-03-07	no assertion criteria provided	research