ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.2777C>A (p.Ala926Asp) (rs138429045)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000245992 SCV000319479 uncertain significance Cardiovascular phenotype 2018-12-11 criteria provided, single submitter clinical testing The p.A926D variant (also known as c.2777C>A), located in coding exon 21 of the FBN2 gene, results from a C to A substitution at nucleotide position 2777. The alanine at codon 926 is replaced by aspartic acid, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659607 SCV000781446 likely benign Connective tissue disease 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV001315396 SCV001505967 uncertain significance Congenital contractural arachnodactyly 2020-03-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 926 of the FBN2 protein (p.Ala926Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 263934). 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). 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.

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