ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1343T>A (p.Met448Lys) (rs777078540)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000388365 SCV000342405 uncertain significance not provided 2016-06-27 criteria provided, single submitter clinical testing
Invitae RCV000388365 SCV001583711 pathogenic not provided 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 448 of the ABCA4 protein (p.Met448Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is present in population databases (rs777078540, ExAC 0.01%). This variant has been observed in individual(s) with Stargardt disease (PMID: 26593885, 29847635). ClinVar contains an entry for this variant (Variation ID: 288325). 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 expected to disrupt ABCA4 protein function. This variant disrupts the p.Met448 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26593885, 29847635). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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