Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000340892 | SCV000341614 | uncertain significance | not provided | 2016-05-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000794544 | SCV000933958 | uncertain significance | Combined immunodeficiency due to LRBA deficiency | 2024-01-15 | 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 1136 of the LRBA protein (p.Pro1136Leu). This variant is present in population databases (rs113022115, gnomAD 0.1%). This missense change has been observed in individual(s) with clinical features of LRBA-related conditions (PMID: 34093558). ClinVar contains an entry for this variant (Variation ID: 287734). 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 LRBA 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. |
Genetic Services Laboratory, |
RCV001820830 | SCV002068309 | uncertain significance | not specified | 2021-12-14 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the LRBA gene demonstrated a sequence change, c.3407C>T, in exon 23 that results in an amino acid change, p.Pro1136Leu. sequence change has been described in the EXAC database with a low population frequency of 0.11% in the African/African-American subpopulation (dbSNP rs113022115). The p.Pro1136Leu change affects a poorly conserved amino acid residue located in a domain of the LRBA protein that is not known to be functional. The p.Pro1136Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with LRBA-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro1136Leu change remains unknown at this time. |
Ambry Genetics | RCV002521981 | SCV003720136 | uncertain significance | Inborn genetic diseases | 2021-09-27 | criteria provided, single submitter | clinical testing | The c.3407C>T (p.P1136L) alteration is located in exon 23 (coding exon 22) of the LRBA gene. This alteration results from a C to T substitution at nucleotide position 3407, causing the proline (P) at amino acid position 1136 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |