Submissions for variant NM_001386298.1(CIC):c.3407A>G (p.Asn1136Ser)

dbSNP: rs2037753806

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001249731	SCV001423762	likely pathogenic	CIC-related neurodevelopmental disorders	2019-12-06	criteria provided, single submitter	clinical testing	The CIC c.680A>G (p.Asn227Ser) variant, also referred to as c.3407A>G (p.Asn1136Ser), is a missense variant that has been reported in one male in a de novo heterozygous state. This individual had mild intellectual disability and did not have dysmorphic features, had normal genitalia, normal growth, and normal hearing and vision. In addition, no malformations or seizures were noted. Additional clinical feature were not described (Athanasakis et al. 2014). This variant is not found in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Even though clinical evidence for the variant is limited, based on the de novo nature of the variant and absence from population frequency databases, the p.Asn227Ser variant is classified as likely pathogenic for CIC-related neurodevelopmental disorders.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001265571	SCV001443733	likely pathogenic	Intellectual disability, autosomal dominant 45	2019-11-19	criteria provided, single submitter	clinical testing	This variant has been previously reported as a de novo change in a patient with intellectual disability (ID) (PMID: 24307393). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. In silico analyses support a deleterious effect of the c.680A>G, p.Asn227Ser variant on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.680A>G, p.Asn227Ser variant is classified as Likely Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268168	SCV001446882	likely pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001265571	SCV005368396	likely pathogenic	Intellectual disability, autosomal dominant 45	2024-08-23	criteria provided, single submitter	clinical testing	Criteria applied: PS2,PS4_MOD,PM2,PP3
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001265571	SCV005418060	likely pathogenic	Intellectual disability, autosomal dominant 45		criteria provided, single submitter	clinical testing	PM2_Supporting+PP3+PS2+PS4_Supporting