Submissions for variant NM_002547.3(OPHN1):c.1913T>C (p.Leu638Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV003337986	SCV004048469	uncertain significance	X-linked intellectual disability-cerebellar hypoplasia syndrome		criteria provided, single submitter	clinical testing	The missense variant c.1913T>C (p.Leu638Pro) in OPHN1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Leu638Pro variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Leu at position 638 is changed to a Pro changing protein sequence and it might alter its composition and physico-chemical properties. In silico tools predict the variant to be tolerated. The residue is conserved across species. The amino acid change p.Leu638Pro in OPHN1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance
Ambry Genetics	RCV004961271	SCV005464988	uncertain significance	Inborn genetic diseases	2024-06-26	criteria provided, single submitter	clinical testing	The c.1913T>C (p.L638P) alteration is located in exon 21 (coding exon 20) of the OPHN1 gene. This alteration results from a T to C substitution at nucleotide position 1913, causing the leucine (L) at amino acid position 638 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.