Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000194474 | SCV000248984 | pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2014-11-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000194474 | SCV000637992 | pathogenic | Congenital muscular hypertrophy-cerebral syndrome | 2017-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 790 of the SMC1A protein (p.Arg790Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (rs797045993, ExAC no frequency). This variant has been reported as de novo in two individuals affected with Cornelia de Lange syndrome (PMID: 17273969, Invitae). ClinVar contains an entry for this variant (Variation ID: 212267). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |