Submissions for variant NM_000527.5(LDLR):c.166T>C (p.Ser56Pro)

dbSNP: rs878854026

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002229339	SCV000285016	pathogenic	Familial hypercholesterolemia	2022-11-15	criteria provided, single submitter	clinical testing	This variant is also known as p.Ser35Pro. This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 9104431, 17539906, 25463123). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 56 of the LDLR protein (p.Ser56Pro). ClinVar contains an entry for this variant (Variation ID: 237864). For these reasons, this variant has been classified as Pathogenic. 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 LDLR protein function.
LDLR-LOVD, British Heart Foundation	RCV000228737	SCV000294490	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000228737	SCV000583637	pathogenic	Hypercholesterolemia, familial, 1	2017-03-30	criteria provided, single submitter	clinical testing