ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.4217A>G (p.His1406Arg)

dbSNP: rs1660186858
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001324844 SCV001515810 pathogenic not provided 2023-10-23 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 1406 of the ABCA4 protein (p.His1406Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ABCA4-related conditions and/or Stargardt disease (PMID: 21911583, 32845068, 33090715; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1024633). 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. For these reasons, this variant has been classified as Pathogenic.
SingHealth Duke-NUS Institute of Precision Medicine RCV005235564 SCV005881634 likely pathogenic Severe early-childhood-onset retinal dystrophy 2025-02-05 criteria provided, single submitter clinical testing Variant is located in a mutational hotspot where >50% of variants are pathogenic (PM1). Homozygous allele count in gnomAD exomes and genomes are less than 0 (PM2). Another variant at this amino acid residue has been classified as pathogenic (PM5, p.His1406Tyr) . REVEL score is 0.683 (PP3)

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