ClinVar Miner

Submissions for variant NM_015192.4(PLCB1):c.1415A>C (p.Lys472Thr)

gnomAD frequency: 0.00002  dbSNP: rs368448785
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001240338 SCV001413272 uncertain significance Developmental and epileptic encephalopathy, 12 2019-11-13 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 tolerated, 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 PLCB1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with threonine at codon 472 of the PLCB1 protein (p.Lys472Thr). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and threonine.
Ambry Genetics RCV002393616 SCV002697267 uncertain significance Inborn genetic diseases 2020-09-29 criteria provided, single submitter clinical testing The p.K472T variant (also known as c.1415A>C), located in coding exon 14 of the PLCB1 gene, results from an A to C substitution at nucleotide position 1415. The lysine at codon 472 is replaced by threonine, an amino acid with 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. This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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