ClinVar Miner

Submissions for variant NM_020751.3(COG6):c.1149T>G (p.Phe383Leu)

gnomAD frequency: 0.00005  dbSNP: rs886050227
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000366573 SCV000384372 uncertain significance COG6-ongenital 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 RCV001850649 SCV002164696 uncertain significance COG6-ongenital disorder of glycosylation; Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome 2021-12-02 criteria provided, single submitter clinical testing 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 312142). This variant has not been reported in the literature in individuals affected with COG6-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 383 of the COG6 protein (p.Phe383Leu).
Ambry Genetics RCV002522290 SCV003594475 uncertain significance Inborn genetic diseases 2021-11-16 criteria provided, single submitter clinical testing The c.1149T>G (p.F383L) alteration is located in exon 12 (coding exon 12) of the COG6 gene. This alteration results from a T to G substitution at nucleotide position 1149, causing the phenylalanine (F) at amino acid position 383 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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