ClinVar Miner

Submissions for variant NM_018718.3(CEP41):c.1037A>G (p.Gln346Arg)

gnomAD frequency: 0.00002  dbSNP: rs782371437
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001051405 SCV001215558 uncertain significance Joubert syndrome 15 2022-07-05 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 847788). This variant has not been reported in the literature in individuals affected with CEP41-related conditions. This variant is present in population databases (rs782371437, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 346 of the CEP41 protein (p.Gln346Arg).
GeneDx RCV001772257 SCV002002361 uncertain significance not provided 2020-07-15 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002553253 SCV003561036 uncertain significance Inborn genetic diseases 2021-06-30 criteria provided, single submitter clinical testing The c.1037A>G (p.Q346R) alteration is located in exon 11 (coding exon 11) of the CEP41 gene. This alteration results from a A to G substitution at nucleotide position 1037, causing the glutamine (Q) at amino acid position 346 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Joe DiMaggio Children's Hospital, Memorial Healthcare System RCV001051405 SCV001976524 pathogenic Joubert syndrome 15 no assertion criteria provided clinical testing "CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium" (Lee et al. 2012). Lee et al. (2012) reported 8 patients from 3 consanguineous families with Joubert syndrome. All patients had hypotonia, ataxia, psychomotor delay with mental retardation, and the molar tooth sign on brain imaging. Additionally, "Joubert syndrome-15 is an autosomal recessive developmental disorder characterized by ataxia, hypotonia, delayed psychomotor development, and variable mental retardation. Other features, such as polydactyly, breathing abnormalities, and oculomotor apraxia, are variable" (summary by Lee et al., 2012). The c.1037A>G variant in CEP41 been observed in compound heterozygosity with c.1000G>A. As a compound heterozygote in an individual with abnormal brain MRI findings, this variant is classified as pathogenic based on functional studies.

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