Submissions for variant NM_000593.6(TAP1):c.955A>C (p.Ile319Leu)

dbSNP: rs748668600

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002034651	SCV002186656	uncertain significance	MHC class I deficiency	2021-03-24	criteria provided, single submitter	clinical testing	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. This sequence change replaces isoleucine with leucine at codon 379 of the TAP1 protein (p.Ile379Leu). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and leucine. This variant is present in population databases (rs748668600, ExAC 0.002%). This variant has not been reported in the literature in individuals with TAP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001794965	SCV002033933	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001794965	SCV002037849	likely benign	not provided		no assertion criteria provided	clinical testing