Submissions for variant NM_005094.4(SLC27A4):c.1511G>T (p.Arg504Leu)

dbSNP: rs776594920

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003660875	SCV004375964	likely pathogenic	not provided	2023-03-26	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 978727). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 504 of the SLC27A4 protein (p.Arg504Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ichthyosis prematurity syndrome (PMID: 33935161). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 expected to disrupt SLC27A4 protein function. This variant disrupts the p.Arg504 amino acid residue in SLC27A4. Other variant(s) that disrupt this residue have been observed in individuals with SLC27A4-related conditions (PMID: 21450060, 30077338), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001257453	SCV001434011	likely pathogenic	Ichthyosis prematurity syndrome	2020-07-07	no assertion criteria provided	clinical testing