Submissions for variant NM_022726.4(ELOVL4):c.351T>A (p.Asn117Lys)

gnomAD frequency: 0.00031  dbSNP: rs148018494

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000262008	SCV000465642	likely benign	Stargardt disease 3	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Eurofins Ntd Llc (ga)	RCV000595647	SCV000702651	uncertain significance	not provided	2016-11-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765894	SCV000897314	uncertain significance	Spinocerebellar ataxia type 34; Stargardt disease 3; Congenital ichthyosis-intellectual disability-spastic quadriplegia syndrome	2018-10-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000595647	SCV001154832	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	ELOVL4: BP4
Invitae	RCV000595647	SCV001417849	uncertain significance	not provided	2023-12-01	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 117 of the ELOVL4 protein (p.Asn117Lys). This variant is present in population databases (rs148018494, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with ELOVL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 358148). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ELOVL4 protein function with a negative predictive value of 80%. 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.
Ambry Genetics	RCV002524509	SCV003652932	uncertain significance	Inborn genetic diseases	2022-03-14	criteria provided, single submitter	clinical testing	Unlikely to be causative of ELOVL4-related spinocerebellar ataxia (AD) and ELOVL4-related Stargardt macular dystrophy (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.