ClinVar Miner

Submissions for variant NM_000100.3(CSTB):c.169G>A (p.Val57Met) (rs796052394)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187285 SCV000240867 uncertain significance not provided 2014-09-23 criteria provided, single submitter clinical testing p.Val57Met (GTG>ATG): c.169 G>A in exon 3 of the CSTB gene (NM_000100.2). The V57M variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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 V57M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved among mammals and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000542984 SCV000636444 uncertain significance Progressive myoclonic epilepsy 2017-06-24 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 57 of the CSTB protein (p.Val57Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with a CSTB-related disease. ClinVar contains an entry for this variant (Variation ID: 205330). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, this variant has uncertain impact on CSTB function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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