ClinVar Miner

Submissions for variant NM_052867.4(NALCN):c.3542G>A (p.Arg1181Gln)

dbSNP: rs786201003
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals RCV000224736 SCV000599270 pathogenic Congenital contractures of the limbs and face, hypotonia, and developmental delay 2016-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001267339 SCV001445520 pathogenic Inborn genetic diseases 2018-06-19 criteria provided, single submitter clinical testing
Invitae RCV001390781 SCV001592623 pathogenic not provided 2022-08-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 188046). This missense change has been observed in individual(s) with arthrogryposis/congenital contractures, ataxia, developmental delay, facial dysmorphism, and/or hypotonia (PMID: 25683120, 25864427, 26763878). 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 replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1181 of the NALCN protein (p.Arg1181Gln).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001390781 SCV001905593 pathogenic not provided 2021-09-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001390781 SCV002497678 pathogenic not provided 2022-04-01 criteria provided, single submitter clinical testing NALCN: PS2, PM2, PS4:Moderate, PP2, PP3, PS3:Supporting
GeneDx RCV001390781 SCV003842660 pathogenic not provided 2022-09-13 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: 33060286, 28454995, 34370008, 35256540, 31409833, 25864427, 25683120, 26763878)
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000224736 SCV004045798 likely pathogenic Congenital contractures of the limbs and face, hypotonia, and developmental delay 2022-11-07 criteria provided, single submitter clinical testing
CHU Sainte-Justine Research Center, University of Montreal RCV000167764 SCV000207425 likely pathogenic Intellectual disability with episodic ataxia and congenital arthrogryposis 2015-01-01 no assertion criteria provided research
University of Washington Center for Mendelian Genomics, University of Washington RCV000224736 SCV000281697 pathogenic Congenital contractures of the limbs and face, hypotonia, and developmental delay 2015-05-19 no assertion criteria provided research

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