Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000238433 | SCV005375294 | likely benign | Hypercholesterolemia, familial, 1 | 2023-11-07 | reviewed by expert panel | curation | The NM_000527.5 (LDLR):c.48C>A (p.Leu16=) variant is classified as Likely Benign for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP4, BP4 and BP7 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 7 November 2023. The supporting evidence is as follows: PM2: PopMax MAF=0.00006 in Latino population in gnomAD (gnomAD v2.1.1). PP4: Variant meets PM2 and is identified in 1 index case with possible FH by Simon Broome criteria, after alternative causes of high cholesterol were excluded, from PMID 7635461 (Ekstrom et al., 1995), Sweden. BP4: Variant is synonymous and splicing evaluation is required. Functional data on splicing is not available. MES: A) Not on limits. B) Not on limits. Variant is not predicted to alter splicing. SpliceAI did not predict alternative splicing (? score=0). BP7 met: Variant is synonymous and meets BP4. This variant has 2 supporting evidence codes (BP4, BP7) towards Benign, enough to classify as Likely Benign, and only PM2 and PP4 evidence codes towards Pathogenic, not enough for Likely Pathogenic, so we are confident in classifying this variant as Likely Benign. |
LDLR- |
RCV000238433 | SCV000294424 | benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Fundacion Hipercolesterolemia Familiar | RCV000238433 | SCV000607407 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Ambry Genetics | RCV002338777 | SCV002635798 | likely benign | Cardiovascular phenotype | 2023-08-08 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Labcorp Genetics |
RCV003581593 | SCV004298007 | likely benign | Familial hypercholesterolemia | 2023-11-10 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000238433 | SCV004820105 | likely benign | Hypercholesterolemia, familial, 1 | 2023-12-01 | criteria provided, single submitter | clinical testing |