Submissions for variant NM_013386.5(SLC25A24):c.650G>A (p.Arg217His)

dbSNP: rs1553253989

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000508607	SCV000320993	pathogenic	Fontaine progeroid syndrome	2016-10-04	criteria provided, single submitter	clinical testing	The variant was identified as de novo in three independent cases with the syndrome and functional studies have shown a likely altered function of the protein.
Fulgent Genetics, Fulgent Genetics	RCV000508607	SCV000893168	pathogenic	Fontaine progeroid syndrome	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001249454	SCV002097451	pathogenic	not provided	2024-06-06	criteria provided, single submitter	clinical testing	Published functional studies suggest that this variant results in mitochondrial dysfunction (PMID: 29100093, 29100094); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30329211, 30281880, 29100093, 29100094, 21216154, 19731360, 10594888, 31775791, 31231135, 36093452, Pannier2022[Abstract], 37449547, 36647814)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001249454	SCV005833986	pathogenic	not provided	2024-08-04	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 217 of the SLC25A24 protein (p.Arg217His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Fontaine progeroid syndrome (PMID: 29100094, 30329211). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 370032). 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 SLC25A24 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SLC25A24 function (PMID: 29100094). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000508607	SCV000679988	pathogenic	Fontaine progeroid syndrome	2022-10-11	no assertion criteria provided	literature only
GenomeConnect, ClinGen	RCV001249454	SCV001423466	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 08-17-2017 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001249454	SCV002035623	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001249454	SCV002037414	pathogenic	not provided		no assertion criteria provided	clinical testing