ClinVar Miner

Submissions for variant NM_015386.3(COG4):c.539A>G (p.Lys180Arg)

gnomAD frequency: 0.00036  dbSNP: rs138693104
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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 RCV000706177 SCV000835214 uncertain significance COG4-congenital disorder of glycosylation 2024-04-24 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 180 of the COG4 protein (p.Lys180Arg). This variant is present in population databases (rs138693104, 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 COG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 582178). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COG4 protein function with a negative predictive value of 80%. 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 RCV002534458 SCV003739903 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.539A>G (p.K180R) alteration is located in exon 4 (coding exon 4) of the COG4 gene. This alteration results from a A to G substitution at nucleotide position 539, causing the lysine (K) at amino acid position 180 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003420262 SCV004140094 likely benign not provided 2022-07-01 criteria provided, single submitter clinical testing COG4: BP4
GeneDx RCV003420262 SCV005079752 uncertain significance not provided 2023-12-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV005021101 SCV005644370 uncertain significance COG4-congenital disorder of glycosylation; Microcephalic osteodysplastic dysplasia, Saul-Wilson type 2024-01-17 criteria provided, single submitter clinical testing

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