ClinVar Miner

Submissions for variant NM_025114.4(CEP290):c.4268G>A (p.Arg1423His)

gnomAD frequency: 0.00002  dbSNP: rs774025278
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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 RCV001038150 SCV001201603 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis 2022-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1423 of the CEP290 protein (p.Arg1423His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 836925). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CEP290 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.
Ambry Genetics RCV004031064 SCV004926229 uncertain significance Inborn genetic diseases 2022-06-24 criteria provided, single submitter clinical testing The c.4268G>A (p.R1423H) alteration is located in exon 33 (coding exon 32) of the CEP290 gene. This alteration results from a G to A substitution at nucleotide position 4268, causing the arginine (R) at amino acid position 1423 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001273068 SCV001455655 uncertain significance Leber congenital amaurosis 2020-01-24 no assertion criteria provided clinical testing

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