ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.542C>T (p.Ser181Phe) (rs139059149)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724369 SCV000231526 uncertain significance not provided 2017-06-27 criteria provided, single submitter clinical testing
GeneDx RCV000724369 SCV000490862 uncertain significance not provided 2017-07-12 criteria provided, single submitter clinical testing The S181F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in24/10374 (0.2%) alleles from individuals of African background, in large population cohorts (Lek et al., 2016). The S181F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a positionthat is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc RCV000179300 SCV000615827 uncertain significance not specified 2016-08-22 criteria provided, single submitter clinical testing
Invitae RCV000724369 SCV000628911 likely benign not provided 2020-12-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV000717907 SCV000848767 uncertain significance Seizures 2017-01-17 criteria provided, single submitter clinical testing The p.S181F variant (also known as c.542C>T), located in coding exon 6 of the TPP1 gene, results from a C to T substitution at nucleotide position 542. The serine at codon 181 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000724369 SCV001148176 uncertain significance not provided 2018-04-01 criteria provided, single submitter clinical testing

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