Submissions for variant NM_000066.4(C8B):c.967C>T (p.Arg323Trp)

gnomAD frequency: 0.00046  dbSNP: rs141295453

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001027773	SCV001190377	uncertain significance	Type II complement component 8 deficiency	2021-03-30	criteria provided, single submitter	clinical testing	C8B NM_000066.3 exon 7 p.Arg323Trp (c.967C>T): This variant has not been reported in the literature, but is present in 0.08% (26/30614) of South Asian alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-57411632-G-A). This variant amino acid Tryptophan (Trp) is present in the chinchilla and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001528886	SCV002287461	uncertain significance	not provided	2025-01-13	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 323 of the C8B protein (p.Arg323Trp). This variant is present in population databases (rs141295453, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with C8B-related conditions. ClinVar contains an entry for this variant (Variation ID: 827971). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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.
Breakthrough Genomics, Breakthrough Genomics	RCV001528886	SCV005186721	uncertain significance	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528886	SCV001741383	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001528886	SCV001964499	uncertain significance	not provided		no assertion criteria provided	clinical testing