ClinVar Miner

Submissions for variant NM_019032.6(ADAMTSL4):c.2594G>A (p.Arg865His)

gnomAD frequency: 0.00007  dbSNP: rs781691587
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444305 SCV000521346 pathogenic not provided 2025-03-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36284667, 25975359, 28642162, 31589614, 36208099, 37337769, 34818515, 39278391, 38146062, 36729443, 24802351, 26653794)
Labcorp Genetics (formerly Invitae), Labcorp RCV000444305 SCV002206118 pathogenic not provided 2024-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 865 of the ADAMTSL4 protein (p.Arg865His). This variant is present in population databases (rs781691587, gnomAD 0.04%). This missense change has been observed in individual(s) with ectopia lentis (PMID: 24802351, 26653794). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It is commonly reported in individuals of Bukharian Jewish ancestry (PMID: 26653794). This variant is also known as c.2663G>A; p.888R>H. ClinVar contains an entry for this variant (Variation ID: 381746). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ADAMTSL4 protein function. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002506033 SCV002817032 likely pathogenic Ectopia lentis et pupillae; Ectopia lentis 2, isolated, autosomal recessive 2021-12-23 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002293436 SCV004049640 likely pathogenic Ectopia lentis et pupillae 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003338587 SCV004049641 likely pathogenic Ectopia lentis 2, isolated, autosomal recessive 2023-04-11 criteria provided, single submitter clinical testing
Farhud Genetics Clinic, Farhud Genetics Lab RCV003338587 SCV004171105 pathogenic Ectopia lentis 2, isolated, autosomal recessive criteria provided, single submitter clinical testing We found this variant in a 7-year-old girl with Ectopia lentis at a homozygous state.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV003338587 SCV004801146 pathogenic Ectopia lentis 2, isolated, autosomal recessive 2024-03-14 criteria provided, single submitter research
GeneReviews RCV002293436 SCV002587001 not provided Ectopia lentis et pupillae no assertion provided literature only

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