ClinVar Miner

Submissions for variant NM_153026.3(PRICKLE1):c.824C>T (p.Thr275Met) (rs559947948)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725886 SCV000340252 uncertain significance not provided 2016-03-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000157058 SCV000896311 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000725886 SCV000242351 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the PRICKLE1 gene. The T275M variant has been reported previously in an individual with lumbosacral myelomeningocele, hydrocephalus, Chiari type II malformation, and tethered cord (Bosoi et al., 2011). However, this variant has not been reported in association with epilepsy. The T275M variant is observed in 13/34074 (0.04%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). The T275M 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000157058 SCV000551470 uncertain significance Progressive myoclonus epilepsy with ataxia 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 275 of the PRICKLE1 protein (p.Thr275Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs559947948, ExAC 0.03%). This variant has been reported in an individual with a neural tube defect, but this individual did not carry a second PRICKLE1 variant (PMID: 21901791). ClinVar contains an entry for this variant (Variation ID: 180205). An experimental study has shown that over-expressing this missense change may disrupt embryonic development in zebrafish (PMID: 21901791). In summary, this variant has uncertain impact on PRICKLE1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000157058 SCV000199324 likely pathogenic Progressive myoclonus epilepsy with ataxia 2014-11-17 no assertion criteria provided clinical testing

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