ClinVar Miner

Submissions for variant NM_003640.5(ELP1):c.2825G>A (p.Arg942Gln) (rs149845612)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000757401 SCV000291942 uncertain significance not provided 2017-01-26 criteria provided, single submitter clinical testing The R942Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project. The R942Qvariant is a semi-conservative amino acid substitution, which may impact secondary protein structureas these residues differ in some properties. This substitution occurs at a position that is conservedacross species and in silico analysis predicts this variant is probably damaging to the proteinstructure/function. Based on the currently available information, it is unclear whether this variant is apathogenic variant or a rare benign variant.
Invitae RCV000757401 SCV000626017 uncertain significance not provided 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 942 of the ELP1 protein (p.Arg942Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs149845612, ExAC 0.09%). This variant has been reported in an individual affected with hereditary motor neuropathy and in an individual affected with Charcot-Marie-Tooth disease (PMID: 26392352). ClinVar contains an entry for this variant (Variation ID: 242293). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757401 SCV000885605 benign not provided 2017-06-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001166669 SCV001329067 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.
Natera, Inc. RCV001166669 SCV001461192 benign Familial dysautonomia 2020-05-30 no assertion criteria provided clinical testing

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