Submissions for variant NM_000372.5(TYR):c.803TCT[1] (p.Phe269del)

dbSNP: rs1064796028

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478390	SCV000572394	likely pathogenic	not provided	2016-12-22	criteria provided, single submitter	clinical testing	The c.806_808delTCT variant in the TYR gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.806_808delTCT variant causes an in-frame deletion of one amnio acid, Phenylalanine 269, denoted p.Phe269del. The c.806_808delTCT variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This deletion occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the deletion is damaging to the protein structure/function. We interpret c.806_808delTCT as a likely pathogenic variant.
Invitae	RCV000478390	SCV002288187	uncertain significance	not provided	2022-05-12	criteria provided, single submitter	clinical testing	This variant, c.806_808del, results in the deletion of 1 amino acid(s) of the TYR protein (p.Phe269del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with oculocutaneous albinism (PMID: 27734839). ClinVar contains an entry for this variant (Variation ID: 422828). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.