Submissions for variant NM_001258392.3(CLPB):c.989C>T (p.Ala330Val)

gnomAD frequency: 0.00045  dbSNP: rs144942416

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000796481	SCV000935996	uncertain significance	3-methylglutaconic aciduria, type VIIB	2025-01-05	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 360 of the CLPB protein (p.Ala360Val). This variant is present in population databases (rs144942416, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with CLPB-related conditions. ClinVar contains an entry for this variant (Variation ID: 642926). 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 disruptive. 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.
GeneDx	RCV003128700	SCV003805489	uncertain significance	not provided	2023-02-24	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
PreventionGenetics, part of Exact Sciences	RCV003947986	SCV004765685	likely benign	CLPB-related disorder	2022-07-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).