Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000381095 | SCV000476318 | uncertain significance | ABCA1-Related Disorders | 2017-04-27 | criteria provided, single submitter | clinical testing | The ABCA1 c.1769G>C (p.Trp590Ser) missense variant is also referred to in the literature as p.Trp530Ser. The variant has been identified in a compound heterozygous state in one individual with Tangier disease who exhibited severely reduced HDL-C levels (Bodzioch et al. 1999). Family studies showed that the patient's father, son, and granddaughter were heterozygous for the p.Trp590Ser variant and also exhibited subnormal HDL-C levels. The p.Trp590Ser variant was absent from 200 control chromosomes (Bodzioch et al. 1999) and is reported at a frequency of 0.00060 in the European (Finnish) population of the Exome Aggregation Consortium. Functional studies indicate that the p.Trp590Ser variant significantly decreases cholesterol and phospholipid efflux but does not significantly impair apoA-I binding (Vaughan et al. 2009; Nagao et al. 2009; Kim et al. 2011; Wang et al. 2013). The evidence for this variant is limited. Therefore, the p.Trp590Ser variant is classified as a variant of unknown significance but suspicious for pathogenicity for ABCA1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
Mayo Clinic Laboratories, |
RCV001509362 | SCV001716021 | uncertain significance | not provided | 2020-05-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001509362 | SCV004264368 | uncertain significance | not provided | 2023-03-19 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects ABCA1 function (PMID: 12509412, 16873719, 18776170, 24097981). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 9490). This variant is also known as G1709C, Trp530Ser. This missense change has been observed in individual(s) with Tangier disease (PMID: 10431237). This variant is present in population databases (rs137854496, gnomAD 0.03%). This sequence change replaces tryptophan, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 590 of the ABCA1 protein (p.Trp590Ser). |
OMIM | RCV000010098 | SCV000030319 | pathogenic | Tangier disease | 1999-08-01 | no assertion criteria provided | literature only |