Submissions for variant NM_000527.5(LDLR):c.491T>C (p.Leu164Pro)

dbSNP: rs879254544

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000238579	SCV000294739	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Color Diagnostics, LLC DBA Color Health	RCV001186869	SCV001353459	uncertain significance	Familial hypercholesterolemia	2020-03-24	criteria provided, single submitter	clinical testing	This missense variant (also known as p.Leu143Pro in the mature protein) replaces leucine with proline at codon 164 of the LDLR protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with familial hypercholesterolemia (PMID: 15823276). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV003221883	SCV003918060	likely pathogenic	not provided	2023-04-01	criteria provided, single submitter	clinical testing	LDLR: PM1, PM2, PM3:Supporting, PP4