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

Total submissions: 5

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