ClinVar Miner

Submissions for variant NM_001543.5(NDST1):c.1831G>A (p.Gly611Ser)

gnomAD frequency: 0.00001  dbSNP: rs606231459
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000148928 SCV001467757 pathogenic Intellectual disability, autosomal recessive 46 2020-12-03 criteria provided, single submitter clinical testing Variant summary: NDST1 c.1831G>A (p.Gly611Ser) results in a non-conservative amino acid change located in the Sulfotransferase domain (IPR000863) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250738 control chromosomes (gnomAD). c.1831G>A has been reported in the literature as a homozygous mutation in multiple individuals affected with intellectual disability (e.g. Reuter_2014, Martinez_2017). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratoire de Génétique Moléculaire, CHU Bordeaux RCV002279948 SCV002568838 pathogenic not provided criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000148928 SCV002581582 likely pathogenic Intellectual disability, autosomal recessive 46 2022-03-11 criteria provided, single submitter clinical testing
Human Genetics Bochum, Ruhr University Bochum RCV002463649 SCV002758631 likely pathogenic Global developmental delay 2022-02-16 criteria provided, single submitter clinical testing ACMG criteria used to clasify this variant: PS4, PM1, PM2_SUP, PP3
Labcorp Genetics (formerly Invitae), Labcorp RCV002279948 SCV003439241 likely pathogenic not provided 2023-03-23 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NDST1 protein function. ClinVar contains an entry for this variant (Variation ID: 161412). This missense change has been observed in individuals with clinical features of intellectual disability (PMID: 25125150, 27620904; Invitae). This variant is present in population databases (rs606231459, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 611 of the NDST1 protein (p.Gly611Ser).
Institute of Human Genetics, University Hospital Muenster RCV003128390 SCV003804820 likely pathogenic See cases 2022-10-20 criteria provided, single submitter clinical testing ACMG categories: PM2,PM3,PP3,PP5
Revvity Omics, Revvity RCV000148928 SCV003814499 likely pathogenic Intellectual disability, autosomal recessive 46 2022-05-16 criteria provided, single submitter clinical testing
GeneDx RCV002279948 SCV003935846 likely pathogenic not provided 2023-06-21 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25125150, 31589614, 27870114, 27620904, 35887114)
CeGaT Center for Human Genetics Tuebingen RCV002279948 SCV004701944 likely pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing NDST1: PM1, PM2, PM3, PP3
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000148928 SCV005016493 pathogenic Intellectual disability, autosomal recessive 46 2023-11-02 criteria provided, single submitter clinical testing
OMIM RCV000148928 SCV000195816 pathogenic Intellectual disability, autosomal recessive 46 2014-11-01 no assertion criteria provided literature only

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