ClinVar Miner

Submissions for variant NM_020751.3(COG6):c.119A>G (p.His40Arg)

gnomAD frequency: 0.00002  dbSNP: rs148246113
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001337863 SCV001531482 uncertain significance COG6-ongenital disorder of glycosylation; Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 40 of the COG6 protein (p.His40Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs148246113, ExAC 0.04%). This variant has not been reported in the literature in individuals affected with COG6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV003346485 SCV004060281 uncertain significance Inborn genetic diseases 2023-07-05 criteria provided, single submitter clinical testing The c.119A>G (p.H40R) alteration is located in exon 1 (coding exon 1) of the COG6 gene. This alteration results from a A to G substitution at nucleotide position 119, causing the histidine (H) at amino acid position 40 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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