ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.362C>T (p.Pro121Leu)

gnomAD frequency: 0.00002  dbSNP: rs377114983
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000704971 SCV000833947 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 121 of the CHRNA4 protein (p.Pro121Leu). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 581212). This variant has not been reported in the literature in individuals affected with CHRNA4-related conditions. This variant is present in population databases (rs377114983, gnomAD 0.03%).
Ambry Genetics RCV002458305 SCV002616415 uncertain significance Inborn genetic diseases 2020-03-27 criteria provided, single submitter clinical testing The p.P121L variant (also known as c.362C>T), located in coding exon 4 of the CHRNA4 gene, results from a C to T substitution at nucleotide position 362. The proline at codon 121 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003411644 SCV004116333 uncertain significance CHRNA4-related condition 2023-02-21 criteria provided, single submitter clinical testing The CHRNA4 c.362C>T variant is predicted to result in the amino acid substitution p.Pro121Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0040% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-61987348-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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