ClinVar Miner

Submissions for variant NM_006329.3(FBLN5):c.376G>A (p.Val126Met) (rs61734479)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000351722 SCV000389481 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000405354 SCV000389482 likely benign Cutis Laxa, Dominant/Recessive 2016-06-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000506503 SCV000603601 uncertain significance not specified 2016-09-21 criteria provided, single submitter clinical testing
GeneDx RCV000584853 SCV000617176 uncertain significance not provided 2018-11-16 criteria provided, single submitter clinical testing The V126M variant in the FBLN5 gene has previously been reported in both disease and control cohorts (Lotery et al., 2006; Auer-Grumbach et al., 2011; Duvvari et al., 2016). It was first reported in an individual with age-related macular degeneration; however, it was also identified in five controls of Dutch ancestry (Lotery et al., 2006). Similarly, Auer-Grumbach et al. (2011) identified this variant in individuals with age-related macular degeneration, but surmised it to be a rare polymorphism because they also observed it in three control individuals and established non-segregation in at least one family with CMT disease. More recently, Duvvari et al. (2016) reported V126M in a sporadic case of cuticular drusen subtype of age-related macular degeneration. The V126M variant has been observed in 397/124,280 alleles (0.3%) from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016).The V126M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Moreover, transfection of V126M into COS-7 cells showed no significant effect on fibulin-5 protein secretion or quantity (Lotery et al., 2006), and biophysical techniques did not suggest any gross structural changes in association with the V126M variant (Jones et al., 2010).
CeGaT Praxis fuer Humangenetik Tuebingen RCV000584853 SCV000692797 likely benign not provided 2017-10-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000584853 SCV000703268 uncertain significance not provided 2016-12-07 criteria provided, single submitter clinical testing
Invitae RCV000584853 SCV001096520 likely benign not provided 2019-01-23 criteria provided, single submitter clinical testing
OMIM RCV000202603 SCV000257549 pathogenic Age-related macular degeneration 3 2011-06-01 no assertion criteria provided literature only

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