Submissions for variant NM_003640.5(ELP1):c.923T>C (p.Leu308Pro)

gnomAD frequency: 0.00236  dbSNP: rs78135392

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000262689	SCV000476585	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000262689	SCV000604025	uncertain significance	Familial dysautonomia	2020-05-07	criteria provided, single submitter	clinical testing	The ELP1 c.923T>C; p.Leu308Pro variant (rs78135392), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 364578). This variant is found in the African population with an allele frequency of 0.75% (186/24964 alleles, including a single homozygote) in the Genome Aggregation Database. The leucine at codon 308 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Leu308Pro variant is uncertain at this time.
GeneDx	RCV000755553	SCV000715000	likely benign	not provided	2021-04-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000755553	SCV000751667	likely benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000262689	SCV001452216	benign	Familial dysautonomia	2020-05-30	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003932508	SCV004755688	likely benign	ELP1-related disorder	2023-04-26	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).