ClinVar Miner

Submissions for variant NM_000368.5(TSC1):c.110G>A (p.Arg37His)

gnomAD frequency: 0.00004  dbSNP: rs750441497
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001703752 SCV000523132 likely benign not provided 2018-06-26 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28250423)
Invitae RCV000468501 SCV000552379 likely benign Tuberous sclerosis 1 2024-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491924 SCV000579955 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-02 criteria provided, single submitter clinical testing The p.R37H variant (also known as c.110G>A), located in coding exon 2 of the TSC1 gene, results from a G to A substitution at nucleotide position 110. The arginine at codon 37 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000468501 SCV002040184 likely benign Tuberous sclerosis 1 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000491924 SCV002530877 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-13 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV003942369 SCV004757568 uncertain significance TSC1-related disorder 2023-10-31 criteria provided, single submitter clinical testing The TSC1 c.110G>A variant is predicted to result in the amino acid substitution p.Arg37His. This variant has been reported in multiple individuals from a family with autism spectrum disorder; however, the variant is listed as lacking co-segregation between the affected family members (Table S3, Saskin et al. 2017. PubMed ID: 28250423). This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-135802688-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV004000387 SCV004840571 uncertain significance Tuberous sclerosis syndrome 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 37 of the TSC1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TSC1-related disorders in the literature. This variant has been identified in 5/250588 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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