Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000457773 | SCV000541744 | uncertain significance | Beckwith-Wiedemann syndrome | 2018-09-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with serine at codon 191 of the CDKN1C protein (p.Ala191Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 output the following: (SIFT: "Tolerated"; PolyPhen-2: "Possibly-damaging"; Align-GVGD: "Class C0"). The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a CDKN1C-related disease. |