Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051163 | SCV001215304 | uncertain significance | Congenital muscular hypertrophy-cerebral syndrome | 2020-06-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with cysteine at codon 699 of the SMC1A protein (p.Arg699Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant has been observed in individual(s) affected with Cornelia de Lange syndrome (PMID: 28548707, Invitae). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). |
Gene |
RCV003319436 | SCV004023968 | pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28135719, 28191890, 28548707, 33504798, 25533962) |