ClinVar Miner

Submissions for variant NM_030665.4(RAI1):c.2966_2969del (p.Lys989fs)

dbSNP: rs1135401792
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris RCV000496203 SCV000586747 pathogenic Smith-Magenis syndrome 2017-01-06 criteria provided, single submitter clinical testing
GeneDx RCV001008262 SCV001168028 pathogenic not provided 2022-08-12 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28708303)
Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn RCV000496203 SCV002107177 pathogenic Smith-Magenis syndrome 2022-03-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001008262 SCV003461720 pathogenic not provided 2023-10-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys989Serfs*74) in the RAI1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAI1 are known to be pathogenic (PMID: 21857958, 24715852). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a neurodevelopmental condition (PMID: 28708303). ClinVar contains an entry for this variant (Variation ID: 431118). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002527127 SCV003581393 pathogenic Inborn genetic diseases 2021-09-29 criteria provided, single submitter clinical testing The c.2966_2969delAAGA (p.K989Sfs*74) alteration, located in exon 3 (coding exon 1) of the RAI1 gene, consists of a deletion of 4 nucleotides from position 2966 to 2969, causing a translational frameshift with a predicted alternate stop codon after 74 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This mutation was identified once in a cohort of individuals with presumed genetic neurodevelopmental disorders via whole exome sequencing (Chérot, 2018). Based on the available evidence, this alteration is classified as pathogenic.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV001008262 SCV005199043 pathogenic not provided 2022-07-21 criteria provided, single submitter clinical testing

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