ClinVar Miner

Submissions for variant NM_001039348.3(EFEMP1):c.418C>T (p.Arg140Trp)

dbSNP: rs756065296
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724508 SCV000230984 uncertain significance not provided 2015-01-22 criteria provided, single submitter clinical testing
GeneDx RCV000724508 SCV000618037 uncertain significance not provided 2017-08-11 criteria provided, single submitter clinical testing The R140W variant in the EFEMP1 gene has been reported previously, in the heterozygous state, segregating with autosomal dominant primary open angle glaucoma in an African American family with multiple affected family members (Mackay et al., 2015). The R140W variant is observed in 1/16512 (0.006%) alleles from individuals of South Asian background, in the ExAC dataset (Lek et al., 2016). The R140W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. Transient expression studies showed increased levels of mutant protein in cell lysates compared to wild type (Mackay et al., 2015). We interpret R140W as a variant of uncertain significance.
Blueprint Genetics RCV001075193 SCV001240806 uncertain significance Retinal dystrophy 2018-11-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000724508 SCV001556033 uncertain significance not provided 2022-09-27 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 EFEMP1 function (PMID: 26162006). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 197709). This missense change has been observed in individual(s) with clinical features of glaucoma (PMID: 26162006). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs756065296, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 140 of the EFEMP1 protein (p.Arg140Trp).
Revvity Omics, Revvity RCV003144148 SCV003831817 uncertain significance Doyne honeycomb retinal dystrophy 2021-11-23 criteria provided, single submitter clinical testing
OMIM RCV003891742 SCV004708211 pathogenic Glaucoma 1, open angle, H 2024-03-18 no assertion criteria provided literature only

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