Submissions for variant NM_004525.3(LRP2):c.3498T>G (p.Phe1166Leu)

gnomAD frequency: 0.00001  dbSNP: rs1281511829

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001985520	SCV002246134	uncertain significance	not provided	2022-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1166 of the LRP2 protein (p.Phe1166Leu). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LRP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1461752). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
CeGaT Center for Human Genetics Tuebingen	RCV001985520	SCV005051384	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	LRP2: PM2
Breakthrough Genomics, Breakthrough Genomics	RCV001985520	SCV005188026	uncertain significance	not provided		criteria provided, single submitter	not provided
Fulgent Genetics, Fulgent Genetics	RCV005025537	SCV005654867	uncertain significance	Donnai-Barrow syndrome	2024-01-23	criteria provided, single submitter	clinical testing