Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001902063 | SCV002127718 | uncertain significance | COG6-congenital disorder of glycosylation; Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome | 2020-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with tyrosine at codon 341 of the COG6 protein (p.Asn341Tyr). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and tyrosine. This variant is present in population databases (rs201922229, ExAC 0.03%). This variant has not been reported in the literature in individuals with COG6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV004980800 | SCV005557846 | uncertain significance | Inborn genetic diseases | 2024-08-14 | criteria provided, single submitter | clinical testing | The c.1021A>T (p.N341Y) alteration is located in exon 11 (coding exon 11) of the COG6 gene. This alteration results from a A to T substitution at nucleotide position 1021, causing the asparagine (N) at amino acid position 341 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |