Submissions for variant NM_153603.4(COG7):c.1499A>G (p.Tyr500Cys)

gnomAD frequency: 0.00014  dbSNP: rs146603761

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001320112	SCV001510886	uncertain significance	COG7 congenital disorder of glycosylation	2022-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 500 of the COG7 protein (p.Tyr500Cys). This variant is present in population databases (rs146603761, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with COG7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1020522). 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 COG7 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.
Fulgent Genetics, Fulgent Genetics	RCV001320112	SCV002793357	uncertain significance	COG7 congenital disorder of glycosylation	2021-12-09	criteria provided, single submitter	clinical testing
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust	RCV001320112	SCV003853448	uncertain significance	COG7 congenital disorder of glycosylation	2023-03-23	criteria provided, single submitter	clinical testing