Submissions for variant NM_014467.3(SRPX2):c.248T>C (p.Leu83Pro)

gnomAD frequency: 0.00007  dbSNP: rs141168255

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766864	SCV000243209	uncertain significance	not provided	2015-09-18	criteria provided, single submitter	clinical testing	p.Leu83Pro (CTG>CCG): c.248 T>C in exon 4 o the SRPX2 gene (NM_014467.2) The L83P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The L83P variant was not observed with any significant frequency in approximately 5,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The L83P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a highly conserved position in the predicted Sushi 1 domain of the SRPX2 protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Athena Diagnostics Inc	RCV000189566	SCV000615508	uncertain significance	not specified	2017-03-07	criteria provided, single submitter	clinical testing
Invitae	RCV001214148	SCV001385817	uncertain significance	Rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked	2020-10-01	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SRPX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 207388). This variant is present in population databases (rs141168255, ExAC 0.006%). This sequence change replaces leucine with proline at codon 83 of the SRPX2 protein (p.Leu83Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
CeGaT Center for Human Genetics Tuebingen	RCV000766864	SCV004167229	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	SRPX2: BS2