ClinVar Miner

Submissions for variant NM_001174147.2(LMX1B):c.706G>C (p.Ala236Pro)

dbSNP: rs1588307140
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV001254094 SCV001430014 pathogenic Nail-patella syndrome 2020-07-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001388093 SCV001588942 pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 236 of the LMX1B protein (p.Ala236Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of nail-patella syndrome (PMID: 9837817; Invitae). This variant is also known as p.Ala213Pro. ClinVar contains an entry for this variant (Variation ID: 976712). 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 expected to disrupt LMX1B protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects LMX1B function (PMID: 9837817). For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology RCV001254094 SCV002557005 pathogenic Nail-patella syndrome 2020-12-11 criteria provided, single submitter clinical testing
GeneDx RCV001388093 SCV002599632 pathogenic not provided 2023-06-23 criteria provided, single submitter clinical testing Reported in unrelated individuals with nail-patella syndrome in the published literature (McIntosh et al., 1998); Published functional studies demonstrate A236P impairs LMX1B transactivation and acts through a haploinsufficiency mechanism (Dreyer et al., 2000); Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.637 G>C p.A213P using alternate nomenclature; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32963778, 10767331, 9837817)
Fulgent Genetics, Fulgent Genetics RCV002485994 SCV002784339 pathogenic Nail-patella syndrome; Nail-patella-like renal disease 2021-08-13 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.