Submissions for variant NM_002547.3(OPHN1):c.1856C>T (p.Pro619Leu)

gnomAD frequency: 0.00002  dbSNP: rs1175919760

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001839264	SCV002099240	uncertain significance	X-linked intellectual disability-cerebellar hypoplasia syndrome	2021-04-22	criteria provided, single submitter	clinical testing	The maternally inherited hemizygous c.1856C>T (p.Pro619Leu)missense variant identified in the OPHN1 gene has not been reported in affected individuals in the literature. The variant has 0.00001798 allele frequency in the gnomAD(v3) database (2 out of 111,226 alleles, 1 hemizygote) suggesting it is not a common benign variant in the populations represented in that database. In silico tools provide conflicting predictions about potential pathogenicity of this variant. Based on the available evidence, the maternally inherited hemizygousc.1856C>T (p.Pro619Leu) missense variant identified in the OPHN1 gene is reported as a variant of uncertain significance.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001839264	SCV004809892	uncertain significance	X-linked intellectual disability-cerebellar hypoplasia syndrome	2024-04-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004953121	SCV005464990	uncertain significance	Inborn genetic diseases	2024-09-18	criteria provided, single submitter	clinical testing	The c.1856C>T (p.P619L) alteration is located in exon 21 (coding exon 20) of the OPHN1 gene. This alteration results from a C to T substitution at nucleotide position 1856, causing the proline (P) at amino acid position 619 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.