Submissions for variant NM_003640.5(ELP1):c.1213C>T (p.Arg405Trp)

gnomAD frequency: 0.00076  dbSNP: rs139703788

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000630703	SCV000751669	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000780354	SCV000917544	uncertain significance	not specified	2017-11-06	criteria provided, single submitter	clinical testing	Variant summary: The IKBKAP c.1213C>T (p.Arg405Trp) variant involves the alteration of a conserved nucleotide. 3/3 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 236/277108 control chromosomes at a frequency of 0.0008517, which does not exceed the estimated maximal expected allele frequency of a pathogenic IKBKAP variant (0.001838). However, one subpopulation (Ashkenazi Jewish) has an allele frequency that is approximately 2 times above the maximal expected allele frequency, and two homozygous controls individuals of South Asian descent have been identified, suggesting a benign impact for the variant. One clinical diagnostic laboratories/reputable databases classified this variant as one of uncertain significance. Taken together, this variant is classified as VUS-possibly benign.
CeGaT Center for Human Genetics Tuebingen	RCV000630703	SCV001249917	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001168463	SCV001331054	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.
GeneDx	RCV000630703	SCV001789525	likely benign	not provided	2019-05-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26392352, 25203624)
Ambry Genetics	RCV000780354	SCV002756297	likely benign	not specified	2022-02-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc.	RCV001276240	SCV001462245	likely benign	Hereditary sensory and autonomic neuropathy	2020-04-16	no assertion criteria provided	clinical testing