Submissions for variant NM_015192.4(PLCB1):c.31T>G (p.Leu11Val)

gnomAD frequency: 0.00001  dbSNP: rs759794686

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001142334	SCV001302768	uncertain significance	Developmental and epileptic encephalopathy, 12	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001142334	SCV001421209	uncertain significance	Developmental and epileptic encephalopathy, 12	2021-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with valine at codon 11 of the PLCB1 protein (p.Leu11Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs759794686, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with PLCB1-related conditions. 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 tolerated. 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.
Ambry Genetics	RCV002320374	SCV002609152	uncertain significance	Inborn genetic diseases	2017-09-06	criteria provided, single submitter	clinical testing	The p.L11V variant (also known as c.31T>G), located in coding exon 1 of the PLCB1 gene, results from a T to G substitution at nucleotide position 31. The leucine at codon 11 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.