Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA040016

252295 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 08edf0a6-3b51-4484-b172-bc1e18ae8e44

Approved on: 2022-08-26

Published on: 2022-12-23

HGVS expressions

NM_000527.5:c.2375T>C

NM_000527.5(LDLR):c.2375T>C (p.Ile792Thr)

NC_000019.10:g.11128071T>C

CM000681.2:g.11128071T>C

NC_000019.9:g.11238747T>C

CM000681.1:g.11238747T>C

NC_000019.8:g.11099747T>C

NG_009060.1:g.43691T>C

ENST00000558518.6:c.2375T>C

ENST00000252444.9:n.2629T>C

ENST00000455727.6:c.1871T>C

ENST00000535915.5:c.2252T>C

ENST00000545707.5:c.1841T>C

ENST00000557933.5:c.2375T>C

ENST00000558013.5:c.2375T>C

ENST00000558518.5:c.2375T>C

ENST00000560628.1:n.108+417T>C

NM_000527.4:c.2375T>C

NM_001195798.1:c.2375T>C

NM_001195799.1:c.2252T>C

NM_001195800.1:c.1871T>C

NM_001195803.1:c.1841T>C

NM_001195798.2:c.2375T>C

NM_001195799.2:c.2252T>C

NM_001195800.2:c.1871T>C

NM_001195803.2:c.1841T>C

Uncertain Significance

PP3

PS3 PM5 PM2

Evidence Links 0

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

The NM_000527.5 (LDLR):c.2375T>C (p. Ile792Thr) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PP3) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PP3: REVEL = 0.773. PM2 not met: PopMax MAF = 0.00056 in Latino population in gnomAD (gnomAD version: 2.1.1). PP4, PS4 not applicable: Variant did not meet PM2. PS3 not met: Functional data is not available. PM5 not met: There is one other variant in the same codon: LDLR: NM_000527:c.2374A>T (p.Ile792Phe) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

PP3

REVEL = 0.773.

PS3

Functional data is not available.

PM5

There is one other variant in the same codon: LDLR: NM_000527:c.2374A>T (p.Ile792Phe) is classified as Uncertain significance - insufficient evidence by these guidelines. Therefore PM5 is not met.

PM2

PopMax MAF = 0.00056 in Latino population in gnomAD (gnomAD version: 2.1.1).

Curation History

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. If you have questions about the information contained on this website, please see a health care professional.