ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.896T>C (p.Leu299Pro)

gnomAD frequency: 0.00014  dbSNP: rs142735836
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000707323 SCV000836414 uncertain significance Congenital myasthenic syndrome 4A 2022-09-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 299 of the CHRNE protein (p.Leu299Pro). This variant is present in population databases (rs142735836, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 583083). 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 disruptive. 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.
Illumina Laboratory Services, Illumina RCV001126039 SCV001285190 uncertain significance Congenital myasthenic syndrome 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.
Fulgent Genetics, Fulgent Genetics RCV002477635 SCV002786471 uncertain significance Congenital myasthenic syndrome 4A; Congenital myasthenic syndrome 4C; Congenital myasthenic syndrome 4B 2022-03-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003144572 SCV003830619 uncertain significance not provided 2019-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165933 SCV003873998 uncertain significance Inborn genetic diseases 2023-03-06 criteria provided, single submitter clinical testing Unlikely to be causative of CHRNE-related congenital myasthenic syndrome type 4A (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001126039 SCV002093407 uncertain significance Congenital myasthenic syndrome 2019-10-28 no assertion criteria provided clinical testing

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