ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.3259G>A (p.Ala1087Thr)

gnomAD frequency: 0.00006  dbSNP: rs61749203
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000339347 SCV000476552 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001201382 SCV000626021 uncertain significance not provided 2022-08-02 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1087 of the ELP1 protein (p.Ala1087Thr). This variant is present in population databases (rs61749203, gnomAD 0.007%). 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: 364561). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
GeneDx RCV001201382 SCV001822739 uncertain significance not provided 2021-01-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001789773 SCV002032282 uncertain significance Medulloblastoma 2021-11-11 criteria provided, single submitter clinical testing The ELP1 c.3259G>A (p.Ala1087Thr) missense change has a maximum subpopulation frequency of 0.0097% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/9-111644431-C-T?dataset=gnomad_r2_1). Five of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with a personal or family history of medulloblastoma. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4
Ambry Genetics RCV004022093 SCV002755217 uncertain significance not specified 2023-12-15 criteria provided, single submitter clinical testing The c.3259G>A (p.A1087T) alteration is located in exon 30 (coding exon 29) of the IKBKAP gene. This alteration results from a G to A substitution at nucleotide position 3259, causing the alanine (A) at amino acid position 1087 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002502402 SCV002786223 uncertain significance Medulloblastoma; Familial dysautonomia 2021-10-03 criteria provided, single submitter clinical testing
Natera, Inc. RCV000339347 SCV001461188 uncertain significance Familial dysautonomia 2020-01-17 no assertion criteria provided clinical testing

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