Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000725899 | SCV000340342 | uncertain significance | not provided | 2016-03-05 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics Inc | RCV000287239 | SCV000614453 | uncertain significance | not specified | 2016-12-12 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000725899 | SCV000885914 | likely benign | not provided | 2018-04-20 | criteria provided, single submitter | clinical testing | The c.434C>T; p.Thr145Met variant (rs45604240, ClinVar variant ID 286781) was detected in one individual among the control cohort in a screen for PINK1 pathogenic variants (Marongiu 2008), and a functional study demonstrated that this variant protein retained the wild-type ability to recruit Parkin protein to mitochondria, while known pathogenic variants had lost this activity (Narendra 2013). This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.003% (identified on 7 out of 246,228 chromosomes). The threonine at position 145 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Thr145Met variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, PolyPhen-2: benign). Based on the available information, the p.Thr145Met variant is likely to be benign. |
| Invitae | RCV001037688 | SCV001201114 | uncertain significance | Autosomal recessive early-onset Parkinson disease 6 | 2022-05-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 145 of the PINK1 protein (p.Thr145Met). This variant is present in population databases (rs45604240, gnomAD 0.006%). This missense change has been observed in individual(s) with parkinsonism (PMID: 18685134). ClinVar contains an entry for this variant (Variation ID: 286781). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect PINK1 function (PMID: 23459931). 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. |
| Illumina Laboratory Services, |
RCV001037688 | SCV001256502 | uncertain significance | Autosomal recessive early-onset Parkinson disease 6 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |