ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.1865C>T (p.Pro622Leu)

gnomAD frequency: 0.00008  dbSNP: rs767679115
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001342167 SCV001536079 uncertain significance Hereditary spastic paraplegia 47 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 622 of the AP4B1 protein (p.Pro622Leu). This variant is present in population databases (rs767679115, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with AP4B1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1038811). 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 AP4B1 protein function with a negative predictive value of 80%. 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 RCV001507968 SCV001713834 uncertain significance not provided 2020-04-20 criteria provided, single submitter clinical testing
Ambry Genetics RCV002546949 SCV003678317 uncertain significance Inborn genetic diseases 2024-09-04 criteria provided, single submitter clinical testing The c.1865C>T (p.P622L) alteration is located in exon 11 (coding exon 10) of the AP4B1 gene. This alteration results from a C to T substitution at nucleotide position 1865, causing the proline (P) at amino acid position 622 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001342167 SCV004050633 uncertain significance Hereditary spastic paraplegia 47 2023-04-11 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.