ClinVar Miner

Submissions for variant NM_002501.4(NFIX):c.361C>T (p.Arg121Cys) (rs797044911)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190740 SCV000244181 pathogenic Inborn genetic diseases 2013-04-26 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV001250542 SCV001425355 likely pathogenic Marshall-Smith syndrome; Sotos syndrome 2 2020-03-19 criteria provided, single submitter clinical testing This NFIX variant is absent from a large population dataset, and has been reported by a single submitter to ClinVar. A missense variant resulting in a different amino acid substitution at this position (p.Arg121Pro) has also been reported, which was maternally inherited. Three bioinformatic tools queried predict that the p.Arg121Cys substitution would be damaging. The arginine residue at this position is evolutionarily conserved across all species assessed except chimp, which has a proline at this position. Additionally, bioinformatic analysis predicts that this variant would not affect normal exon 2 splicing, although this has not been confirmed experimentally, to our knowledge. This substitution occurs in the N-terminal DNA-binding and dimerization domain of the NFIX protein, where other disease causing variants have been identified. We consider the c.361C>T variant to be likely pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV001270871 SCV001451648 likely pathogenic Marshall-Smith syndrome 2019-01-08 criteria provided, single submitter clinical testing The NFIX c.385C>T (p.Arg129Cys) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found through this search. This variant is not reported in the Genome Aggregation Database in a region of good sequence coverage, so the variant is presumed to be rare. Functional studies of this variant have not been conducted, but it is located in the DNA binding domain (Priolo et al. 2018). Based on its rarity, location, and de novo occurrence, the p.Arg129Cys variant is classified as likely pathogenic for Marshall-Smith syndrome.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001311170 SCV001501241 pathogenic not provided 2020-11-01 criteria provided, single submitter clinical testing

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