Submissions for variant NM_000372.5(TYR):c.1366+4A>G

gnomAD frequency: 0.00175  dbSNP: rs61754398

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000418890	SCV000515218	uncertain significance	not specified	2016-01-13	criteria provided, single submitter	clinical testing	The c.1366+4A>G variant in the TYR gene has been reported previously in the heterozygous state in an individual with oculocutaneous albinism type 1B (Hutton et al., 2008). This variant reduces the quality of the splice donor site in intron 4, and is expected to cause abnormal gene splicing. However, the NHLBI Exome Sequencing Project reports that c.1366+4A>G was observed in 23/8592 alleles (0.26%) from individuals of European American ancestry, including one homozygous individual within this control population. Based on the currently available data, we interpret c.1366+4A>G as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000765024	SCV000896209	uncertain significance	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
Illumina Laboratory Services, Illumina	RCV001111957	SCV001269567	uncertain significance	Oculocutaneous albinism	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085923	SCV001672458	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001588917	SCV001821913	uncertain significance	Tyrosinase-negative oculocutaneous albinism	2021-07-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085923	SCV005050350	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	TYR: PM2, BP4
Retina International	RCV000085923	SCV000118066	not provided	not provided		no assertion provided	not provided
Clinical Genetics, Academic Medical Center	RCV000085923	SCV001923462	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000085923	SCV001965569	uncertain significance	not provided		no assertion criteria provided	clinical testing