Submissions for variant NM_000384.3(APOB):c.6659T>C (p.Val2220Ala)

gnomAD frequency: 0.00003  dbSNP: rs374736992

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520891	SCV000620067	uncertain significance	not provided	2022-02-10	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Illumina Laboratory Services, Illumina	RCV001142366	SCV001302800	uncertain significance	Familial hypobetalipoproteinemia 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001142367	SCV001302801	uncertain significance	Hypercholesterolemia, autosomal dominant, type B	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001858001	SCV002167689	likely benign	Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1	2023-12-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002367740	SCV002663269	uncertain significance	Cardiovascular phenotype	2021-07-30	criteria provided, single submitter	clinical testing	The p.V2220A variant (also known as c.6659T>C), located in coding exon 26 of the APOB gene, results from a T to C substitution at nucleotide position 6659. The valine at codon 2220 is replaced by alanine, an amino acid with 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.