ClinVar Miner

Submissions for variant NM_006265.2(RAD21):c.1349G>A (p.Arg450His) (rs1051321465)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494611 SCV000583067 uncertain significance not specified 2017-05-22 criteria provided, single submitter clinical testing The R450H variant in the RAD21 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R450H variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R450H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R450H as a variant of uncertain significance.
Geisinger Autism and Developmental Medicine Institute,Geisinger Health System RCV000678348 SCV000804412 uncertain significance Cornelia de Lange syndrome 4 2017-05-26 criteria provided, single submitter provider interpretation This 9 year old female with an intellectual disability was found to carry a missense variant in the RAD21 gene. Inheritance is unknown, as is paternal family history. She is non-dysmorphic, normocephalic, and does not have any congenital anomalies. While variable expressivity has been noted in some individuals with Cornelia de Lange Syndrome 4, this patient's lack of growth retardation, skeletal anomalies, and facial dysmorphism make it more unlikely that this is a causative variant for her intellectual disability. The variant is absent from population databases and has not been reported in any individuals with Cornelia de Lange syndrome, to our knowledge. Computational prediction models are inconsistent.

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