ClinVar Miner

Submissions for variant NM_018714.3(COG1):c.1243G>C (p.Glu415Gln)

gnomAD frequency: 0.00021  dbSNP: rs142830395
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001123705 SCV001282558 uncertain significance COG1 congenital disorder of glycosylation 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001123705 SCV001384144 uncertain significance COG1 congenital disorder of glycosylation 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 415 of the COG1 protein (p.Glu415Gln). This variant is present in population databases (rs142830395, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 889657). 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 COG1 protein function. 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.
Baylor Genetics RCV001123705 SCV001529188 uncertain significance COG1 congenital disorder of glycosylation 2018-09-10 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV002556675 SCV003736151 uncertain significance Inborn genetic diseases 2021-06-22 criteria provided, single submitter clinical testing The c.1243G>C (p.E415Q) alteration is located in exon 6 (coding exon 6) of the COG1 gene. This alteration results from a G to C substitution at nucleotide position 1243, causing the glutamic acid (E) at amino acid position 415 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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