ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.3280A>G (p.Arg1094Gly) (rs146440397)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000659118 SCV000291943 uncertain significance not provided 2018-07-13 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the IKBKAP gene. The R1094G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1094G variant is observed in 101/66402 (0.2%) alleles from individuals of European non-Finnish background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1094G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000659118 SCV000626022 benign not provided 2019-12-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000659118 SCV000705489 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000659118 SCV000780931 uncertain significance not provided 2018-01-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001166178 SCV000884035 uncertain significance Familial dysautonomia 2020-04-09 criteria provided, single submitter clinical testing The p.Arg1094Gly variant (rs146440397) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.2 percent in the European Non-Finnish population (identified on 215 out of 126,458 chromosomes) and has been reported to the ClinVar database (Variation ID: 242294). The arginine at position 1094 is highly conserved up to C. elegans considering 13 species (Alamut v2.11) and computational analyses of the effects of the p.Arg1094Gly variant on protein structure and function provide conflicting results (SIFT: tolerated, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Arg1094Gly variant with certainty.
Illumina Clinical Services Laboratory,Illumina RCV001166178 SCV001328519 uncertain significance Familial dysautonomia 2018-01-13 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.
Natera, Inc. RCV001166178 SCV001461187 uncertain significance Familial dysautonomia 2020-01-17 no assertion criteria provided clinical testing

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