ClinVar Miner

Submissions for variant NM_001242896.3(DEPDC5):c.829C>T (p.Leu277Phe)

dbSNP: rs778656662
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001304151 SCV001493422 uncertain significance Familial focal epilepsy with variable foci 2023-01-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 277 of the DEPDC5 protein (p.Leu277Phe). This variant is present in population databases (rs778656662, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DEPDC5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007024). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.
Revvity Omics, Revvity RCV003490175 SCV003829001 uncertain significance not provided 2019-03-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV003166719 SCV003881403 uncertain significance Inborn genetic diseases 2023-03-14 criteria provided, single submitter clinical testing The c.829C>T (p.L277F) alteration is located in exon 13 (coding exon 12) of the DEPDC5 gene. This alteration results from a C to T substitution at nucleotide position 829, causing the leucine (L) at amino acid position 277 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV004546630 SCV005042908 uncertain significance Epilepsy, familial focal, with variable foci 1 criteria provided, single submitter clinical testing The missense c.829C>Tp.Leu277Phe variant in DEPDC5 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has been reported with allele frequency of 0.004% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid change p.Leu277Phe in DEPDC5 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Leu at position 277 is changed to a Phe changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance VUS.
GeneDx RCV003490175 SCV005690345 uncertain significance not provided 2024-08-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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