ClinVar Miner

Submissions for variant NM_003073.5(SMARCB1):c.110G>A (p.Arg37His) (rs398122368)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000262341 SCV000329523 pathogenic not provided 2016-09-07 criteria provided, single submitter clinical testing The R37H pathogenic variant in the SMARCB1 gene has been observed in at least one individual with features suggestive of Kleefstra syndrome (Kleefstra et al., 2012; Kosho et al., 2014). The R37H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R37H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species and is located in the DNA binding domain (Allen et al., 2015). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R37H as a pathogenic variant.
Baylor Genetics RCV000074462 SCV000807306 uncertain significance Mental retardation, autosomal dominant 15 2017-09-01 criteria provided, single submitter clinical testing This variant has been previously reported as disease-causing and was found twice in our laboratory de novo: in a 6-year-old male with global delays, autism spectrum, hypotonia, hydrocephalus, VUR, agenesis of the corpus callosum, myopia, pes cavus, elevated free T4; in an 8-year-old female with intellectual disability, behavior problems, hydrocephalus, dysmorphisms, amblyopia, myopic astigmatixm, hypoplastic labia majora, hypertonia, decreased muscle mass, dysphagia, Wilms tumor
SIB Swiss Institute of Bioinformatics RCV000074462 SCV000883290 uncertain significance Mental retardation, autosomal dominant 15 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Uncertain Significance - Insufficient Evidence, for Coffin-Siris syndrome 3, autosomal dominant. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6 => Assumed de novo, but without confirmation of paternity and maternity (https://www.ncbi.nlm.nih.gov/pubmed/22726846).
Baylor Genetics RCV001533133 SCV001748953 pathogenic SMARCB1-related BAFopathy 2021-06-10 criteria provided, single submitter clinical testing
OMIM RCV000074462 SCV000108478 pathogenic Mental retardation, autosomal dominant 15 2012-07-13 no assertion criteria provided literature only

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