ClinVar Miner

Submissions for variant NM_006329.3(FBLN5):c.268G>A (p.Gly90Ser) (rs144288844)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521928 SCV000617418 uncertain significance not provided 2018-08-03 criteria provided, single submitter clinical testing The G90S variant in the FBLN5 gene has previously been reported in two siblings with spinal Charcot-Marie-Tooth as well as three of their relatives who were mildly affected with neurological and/or connective tissue involvement (Auer-Grumbach et al., 2011). G90S was also identified in a patient with age-related macular degeneration from age 79, mild to moderate weakness and wasting in hand and foot muscles, and axonal neuropathy in upper and lower limbs; this patient shared multiple single nucleotide polymorphism markers with the two siblings, suggesting a possible founder effect (Auer-Grumbach et al., 2011). The G90S 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Furthermore, this variant was observed in 71/124,250 (0.06%) alleles from individuals of European (non-Finnish) ancestry and in 22/10,142 (0.2%) alleles from individuals of Ashkenazi Jewish ancestry in large population cohorts (Lek et al., 2016).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Illumina Clinical Services Laboratory,Illumina RCV000288309 SCV000389483 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
OMIM RCV000202614 SCV000257548 pathogenic Age-related macular degeneration 3 2011-06-01 no assertion criteria provided literature only

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