Familial Russell–Silver Syndrome like Phenotype in the PCNA Domain of the CDKN1C Gene, a Further Case

Table 1

Evidence criteria used for classification and strength level of evidence utilised.

Evidence criteria for pathogenicity	Strength level of evidence used	ACMG Code
Cosegregation with disease in multiple affected family members in a gene definitively known to cause disease ()	Strong	PP1
Located in a mutational hot spot and/or critical and well-established functional domain without benign variation	Moderate	PM1
Absent from controls	Moderate	PM2
Missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before	Moderate	PM5
Multiple lines of computational evidence support a deleterious effect on the gene or gene product	Supporting	PP3
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product	Supporting	PS3
The prevalence of the variant in affected individuals is significantly increased compared with the prevalence in controls	Supporting	PS4
Patient’s phenotype or FH highly specific for gene	Supporting	PP4