ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.1073G>A (p.Arg358Gln)

gnomAD frequency: 0.00011  dbSNP: rs139091484
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000360847 SCV000476581 uncertain significance Familial dysautonomia 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.
Invitae RCV000791436 SCV000626001 uncertain significance not provided 2022-08-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 358 of the ELP1 protein (p.Arg358Gln). This variant is present in population databases (rs139091484, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ELP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 364576). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV004022101 SCV002755547 uncertain significance not specified 2022-07-17 criteria provided, single submitter clinical testing The p.R358Q variant (also known as c.1073G>A), located in coding exon 10 of the IKBKAP gene, results from a G to A substitution at nucleotide position 1073. The arginine at codon 358 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002481253 SCV002779845 uncertain significance Medulloblastoma; Familial dysautonomia 2022-01-10 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153567 SCV003843185 uncertain significance Medulloblastoma 2022-12-07 criteria provided, single submitter clinical testing The ELP1 c.1073G>A (p.Arg358Gln) missense change has a maximum subpopulation frequency of 0.045% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with a personal or family history of medulloblastoma. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc. RCV000360847 SCV001458963 uncertain significance Familial dysautonomia 2020-09-16 no assertion criteria provided clinical testing

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