Submissions for variant NM_000548.5(TSC2):c.167A>G (p.Asn56Ser) (rs144165984)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000190009	SCV000243681	likely benign	not specified	2017-01-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000226143	SCV000285256	uncertain significance	Tuberous sclerosis 2	2016-11-28	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine with serine at codon 56 of the TSC2 protein (p.Asn56Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs144165984, ExAC 0.05%) but has not been reported in the literature in individuals with a TSC2-related disease. ClinVar contains an entry for this variant (Variation ID: 161398). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV000571093	SCV000664744	uncertain significance	Hereditary cancer-predisposing syndrome	2016-12-13	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Insufficient or conflicting evidence
CSER_CC_NCGL; University of Washington Medical Center	RCV000148918	SCV000190671	uncertain significance	Tuberous sclerosis syndrome	2014-06-01	no assertion criteria provided	research

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