ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.2630A>G (p.Asn877Ser)

dbSNP: rs1567482364
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000693788 SCV000821671 uncertain significance Tuberous sclerosis 2 2024-08-13 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 877 of the TSC2 protein (p.Asn877Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 572415). 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 not expected to disrupt TSC2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001016173 SCV001177093 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-26 criteria provided, single submitter clinical testing The p.N877S variant (also known as c.2630A>G), located in coding exon 22 of the TSC2 gene, results from an A to G substitution at nucleotide position 2630. The asparagine at codon 877 is replaced by serine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000693788 SCV002040713 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004802371 SCV005427150 uncertain significance Tuberous sclerosis syndrome 2024-06-09 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 877 of the TSC2 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 TSC2-related disorders in the literature. This variant has not been identified 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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