ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4900C>T (p.Arg1634Cys)

dbSNP: rs760457821
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725350 SCV000243711 uncertain significance not provided 2012-11-06 criteria provided, single submitter clinical testing p.Arg1634Cys (CGC>TGC):c.4900 C>T in exon 38 of the TSC2 gene (NM_000548.3)The Arg1634Cys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Arg1634Cys in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a positively charged Arginine residue is replaced by an uncharged Cysteine residue, and the gain of a Cysteine could affect disulfide bond formation in the protein. It alters a position in the GAP-related domain of the tuberin protein near the location of many pathogenic missense mutations; however, this position is not conserved through evolution. Some in silico algorithms predict it Arg1634Cys may be damaging to protein structure/function, while another model indicates it is likely benign. Therefore, based on the currently available information, it is unclear whether Arg1634Cys is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Eurofins Ntd Llc (ga) RCV000725350 SCV000336241 uncertain significance not provided 2015-10-16 criteria provided, single submitter clinical testing
Invitae RCV001314556 SCV001505092 benign Tuberous sclerosis 2 2024-01-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001314556 SCV002040859 uncertain significance Tuberous sclerosis 2 2021-11-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336506 SCV002635821 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-18 criteria provided, single submitter clinical testing The p.R1634C variant (also known as c.4900C>T), located in coding exon 37 of the TSC2 gene, results from a C to T substitution at nucleotide position 4900. The arginine at codon 1634 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001314556 SCV003821610 uncertain significance Tuberous sclerosis 2 2021-05-03 criteria provided, single submitter clinical testing

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