ClinVar Miner

Submissions for variant NM_020366.4(RPGRIP1):c.1059G>C (p.Leu353Phe)

gnomAD frequency: 0.00002  dbSNP: rs756365691
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000396734 SCV000385403 uncertain significance Leber congenital amaurosis 6 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000295356 SCV000385404 uncertain significance Cone-rod dystrophy 13 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001052349 SCV001216556 uncertain significance Cone-rod dystrophy 13; Leber congenital amaurosis 6 2022-06-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 353 of the RPGRIP1 protein (p.Leu353Phe). This variant is present in population databases (rs756365691, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 312785). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Genome-Nilou Lab RCV000396734 SCV002044922 uncertain significance Leber congenital amaurosis 6 2021-11-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000295356 SCV002044933 uncertain significance Cone-rod dystrophy 13 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002522297 SCV003710138 uncertain significance Inborn genetic diseases 2022-06-03 criteria provided, single submitter clinical testing The c.1059G>C (p.L353F) alteration is located in exon 8 (coding exon 8) of the RPGRIP1 gene. This alteration results from a G to C substitution at nucleotide position 1059, causing the leucine (L) at amino acid position 353 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003137915 SCV003811884 uncertain significance not provided 2021-07-09 criteria provided, single submitter clinical testing

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