Submissions for variant NM_000384.3(APOB):c.1975C>T (p.Leu659Phe)

dbSNP: rs1026800482

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002418630	SCV002723524	uncertain significance	Cardiovascular phenotype	2022-06-06	criteria provided, single submitter	clinical testing	The p.L659F variant (also known as c.1975C>T), located in coding exon 14 of the APOB gene, results from a C to T substitution at nucleotide position 1975. The leucine at codon 659 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003989643	SCV004807440	uncertain significance	Familial hypobetalipoproteinemia 1	2024-03-26	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV003989643	SCV005399963	uncertain significance	Familial hypobetalipoproteinemia 1	2021-05-06	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypercholesterolemia 2 (MIM#144010) and hypobetalipoproteinemia (MIM#615558). (I) 0108 - This gene is associated with both recessive and dominant disease. Familial hypercholesterolemia 2 (MIM#144010) is inherited in an autosomal dominant manner, whereas hypobetalipoproteinemia (MIM#615558) is recessive (OMIM). (I) 0112 - The condition associated with this gene has incomplete penetrance (PMID: 24404629). (I) 0200 - Variant is predicted to result in a missense amino acid change from leucine to phenylalanine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated domain of unknown function 1943 (NCBI, DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive as it has been reported only as a VUS (ClinVar, LOVD). (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Clinical Genetics, Academic Medical Center	RCV001701301	SCV001922309	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001701301	SCV001973576	uncertain significance	not provided		no assertion criteria provided	clinical testing