ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.1192G>T (p.Ala398Ser)

gnomAD frequency: 0.00003  dbSNP: rs764079993
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001984054 SCV002286670 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 398 of the CEP290 protein (p.Ala398Ser). This variant is present in population databases (rs764079993, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. ClinVar contains an entry for this variant (Variation ID: 1493024). 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 serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
New York Genome Center RCV002468375 SCV002764546 uncertain significance Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5 2020-12-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV004612081 SCV005105328 uncertain significance Inborn genetic diseases 2024-03-16 criteria provided, single submitter clinical testing The c.1192G>T (p.A398S) alteration is located in exon 14 (coding exon 13) of the CEP290 gene. This alteration results from a G to T substitution at nucleotide position 1192, causing the alanine (A) at amino acid position 398 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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