Submissions for variant NM_000372.5(TYR):c.895C>T (p.Arg299Cys)

dbSNP: rs61754374

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001699704	SCV002032628	pathogenic	not provided	2021-12-08	criteria provided, single submitter	clinical testing	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: 20447099, 19060277, 28451379, 30868578, 30158334, 27593200, 26165494, 25577957, 31077556, 25323826, 31199599, 19865097)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001699704	SCV002229167	pathogenic	not provided	2024-06-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 299 of the TYR protein (p.Arg299Cys). This variant is present in population databases (rs61754374, gnomAD 0.01%). This missense change has been observed in individuals with ocular albinism (PMID: 19060277, 30868578). ClinVar contains an entry for this variant (Variation ID: 1284359). 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 with a positive predictive value of 80%. This variant disrupts the p.Arg299 amino acid residue in TYR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1642278, 28112372, 28266639). 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.
Baylor Genetics	RCV003470878	SCV004207604	pathogenic	SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2023-05-24	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005005268	SCV005631357	pathogenic	Oculocutaneous albinism type 1A; Oculocutaneous albinism type 1B; SKIN/HAIR/EYE PIGMENTATION 3, LIGHT/DARK SKIN	2024-03-20	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001699704	SCV001920220	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699704	SCV001971101	pathogenic	not provided		no assertion criteria provided	clinical testing