ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.1222T>C (p.Trp408Arg) (rs376384105)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000731193 SCV000242367 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing p.Trp408Arg (TGG>CGG): c.1222 T>C in exon 7 of the PRICKLE1 gene (NM_153026.2). The Trp408Arg missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The amino acid substitution is non-conservative as an uncharged, non-polar Tryptophan amino acid residue is replaced by a positively charged, polar Arginine residue. Several in-silico algorithms predict Trp408Arg may be damaging to the structure/function of the protein. However, it alters a position that is not well conserved and to our knowledge, other missense mutations have not been previously reported in this region of the protein. Therefore, based on the currently available information, it is unclear whether Trp408Arg is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Invitae RCV000698134 SCV000826777 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-07-08 criteria provided, single submitter clinical testing This sequence change replaces tryptophan with arginine at codon 408 of the PRICKLE1 protein (p.Trp408Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is present in population databases (rs376384105, ExAC 0.03%). This variant has not been reported in the literature in individuals with PRICKLE1-related disease. ClinVar contains an entry for this variant (Variation ID: 206666). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000720205 SCV000851082 uncertain significance Seizures 2016-06-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000731193 SCV000858976 uncertain significance not provided 2018-01-16 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000698134 SCV000896310 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-10-31 criteria provided, single submitter clinical testing

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