ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1088C>T (p.Pro363Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003324349 SCV004028603 uncertain significance not specified 2023-07-20 criteria provided, single submitter clinical testing Variant summary: RPE65 c.1088C>T (p.Pro363Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251300 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1088C>T in individuals affected with Leber Congenital Amaurosis and no experimental evidence demonstrating its impact on protein function have been reported. One variant affecting the same codon have been classified as pathogenic in ClinVar (c.1087C>A, p.Pro363T- CV ID 13117) and a second variant (c.1088C>G, p.P363R) has been reported in the literature in bi-allelic individuals affected with Leber Congenital Amaurosis (PubMed: 26626312, 30268864, 33173045) suggesting this residue may be critical for the normal function of the protein. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005029982 SCV005660914 likely pathogenic Leber congenital amaurosis 2; Retinitis pigmentosa 20; Retinitis pigmentosa 87 with choroidal involvement 2024-06-10 criteria provided, single submitter clinical testing

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