ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.2498A>C (p.His833Pro)

gnomAD frequency: 0.00012  dbSNP: rs201714373
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001239450 SCV001412325 uncertain significance not provided 2022-08-03 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 833 of the ELP1 protein (p.His833Pro). This variant is present in population databases (rs201714373, gnomAD 0.02%). 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: 965089). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV004034614 SCV002754976 uncertain significance not specified 2023-06-22 criteria provided, single submitter clinical testing The p.H833P variant (also known as c.2498A>C), located in coding exon 22 of the IKBKAP gene, results from an A to C substitution at nucleotide position 2498. The histidine at codon 833 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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 RCV002480786 SCV002790095 uncertain significance Medulloblastoma; Familial dysautonomia 2022-04-15 criteria provided, single submitter clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003325227 SCV004031218 uncertain significance Medulloblastoma 2023-07-06 criteria provided, single submitter clinical testing The ELP1 c.2498A>C (p.His833Pro) missense change has a maximum subpopulation frequency of 0.024% 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. RCV001277385 SCV001464333 uncertain significance Familial dysautonomia 2020-08-21 no assertion criteria provided clinical testing

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