ClinVar Miner

Submissions for variant NM_006329.4(FBLN5):c.178G>C (p.Val60Leu)

gnomAD frequency: 0.00002  dbSNP: rs121434299
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001851678 SCV002269734 uncertain significance not provided 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 60 of the FBLN5 protein (p.Val60Leu). This variant is present in population databases (rs121434299, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FBLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 5477). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change does not substantially affect FBLN5 function (PMID: 16652333, 20007835). 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.
OMIM RCV000005811 SCV000025993 pathogenic Macular degeneration, age-related, 3 2004-07-22 no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV003447069 SCV004174402 uncertain significance Age-related macular degeneration 2016-01-06 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004751203 SCV005353882 uncertain significance FBLN5-related disorder 2024-09-26 no assertion criteria provided clinical testing The FBLN5 c.178G>C variant is predicted to result in the amino acid substitution p.Val60Leu. This variant was reported, heterozygous, in an individual with age-related macular degeneration (Stone et al 2004. PubMed ID: 15269314). This variant is reported in 0.0032% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In vitro functional characterization showed that this variant did not affect the dimerization or the aggregation of fibulin 5 (Jones et al. 2009. PubMed ID: 20007835). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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