Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048385 | SCV001212386 | pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2019-05-16 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 C0"). This variant has been observed to be de novo in individuals with clinical features of Cornelia de Lange syndrome (PMID: 17273969, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with valine at codon 133 of the SMC1A protein (p.Phe133Val). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and valine. |