ClinVar Miner

Submissions for variant NM_000466.3(PEX1):c.1975G>T (p.Val659Phe)

dbSNP: rs193221288
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000284256 SCV000343511 uncertain significance not provided 2017-08-08 criteria provided, single submitter clinical testing
Invitae RCV001243316 SCV001416465 uncertain significance Zellweger spectrum disorders 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 659 of the PEX1 protein (p.Val659Phe). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PEX1-related conditions. ClinVar contains an entry for this variant (Variation ID: 289197). 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 not expected to disrupt PEX1 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000284256 SCV002540874 uncertain significance not provided 2021-10-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002518072 SCV003699464 uncertain significance Inborn genetic diseases 2021-11-16 criteria provided, single submitter clinical testing The c.1975G>T (p.V659F) alteration is located in exon 12 (coding exon 12) of the PEX1 gene. This alteration results from a G to T substitution at nucleotide position 1975, causing the valine (V) at amino acid position 659 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Preventiongenetics, part of Exact Sciences RCV003401268 SCV004120546 uncertain significance PEX1-related condition 2023-02-14 criteria provided, single submitter clinical testing The PEX1 c.1975G>T variant is predicted to result in the amino acid substitution p.Val659Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-92134142-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001243316 SCV002076882 uncertain significance Zellweger spectrum disorders 2018-06-26 no assertion criteria provided clinical testing

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