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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