ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.782T>C (p.Val261Ala)

gnomAD frequency: 0.00002  dbSNP: rs146136938
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000804021 SCV000943911 uncertain significance not provided 2022-06-27 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 261 of the TPP1 protein (p.Val261Ala). This variant is present in population databases (rs146136938, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of TPP1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 649155). 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 expected to disrupt TPP1 protein function. 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.
GeneDx RCV000804021 SCV001777935 uncertain significance not provided 2019-12-04 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002406787 SCV002669258 uncertain significance Inborn genetic diseases 2019-06-24 criteria provided, single submitter clinical testing The p.V261A variant (also known as c.782T>C), located in coding exon 7 of the TPP1 gene, results from a T to C substitution at nucleotide position 782. The valine at codon 261 is replaced by alanine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, alanine is the reference amino acid in other 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.
Natera, Inc. RCV001825589 SCV002094855 uncertain significance Neuronal ceroid lipofuscinosis 2 2021-03-28 no assertion criteria provided clinical testing

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