ClinVar Miner

Submissions for variant NM_001111125.3(IQSEC2):c.1591C>T (p.Arg531Ter)

dbSNP: rs1602284689
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000790432 SCV000929759 likely pathogenic Intellectual disability 2018-07-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001091938 SCV001248230 pathogenic not provided 2017-12-01 criteria provided, single submitter clinical testing
Invitae RCV003117580 SCV003787218 pathogenic Intellectual disability, X-linked 1 2022-11-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 637967). This premature translational stop signal has been observed in individual(s) with clinical features of IQSEC2-related conditions (PMID: 30666632, 33368194). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg531*) in the IQSEC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IQSEC2 are known to be pathogenic (PMID: 21686261, 26793055, 27665735).
GeneDx RCV001091938 SCV003798941 pathogenic not provided 2022-08-02 criteria provided, single submitter clinical testing Nonsense 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33504798, 30666632, 33368194)
Neuberg Centre For Genomic Medicine, NCGM RCV003117580 SCV005061075 pathogenic Intellectual disability, X-linked 1 criteria provided, single submitter clinical testing The observed stop gained variant c.1591C>T(p.Arg531Ter) in IQSEC2 gene has been reported in heterozygous state in individuals affected with intellectual disability (Radley JA, et al., 2019, Lopergolo D, et al., 2021). The c.1591C>T variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic/Likely Pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing (Zerem A, et al., 2016). For these reasons, this variant has been classified as Pathogenic.

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