Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590583 | SCV000695471 | likely pathogenic | Marfan syndrome | 2017-12-12 | criteria provided, single submitter | clinical testing | Variant summary: The FBN1 c.1888A>T (p.Asn630Tyr) variant involves the alteration of a conserved nucleotide that is located within one of the EGF-like calcium-binding domains (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 246208 control chromosomes. To our knowledge, the variant has not been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. However, variants involving the same codon (such as p.Asn630Ile and p.Asn630Lys) have been identified in affected individuals and are classified as pathogenic by another clinical lab (via ClinVar), and other surrounding variants (such as p.G626R, p.R627C, p.C628Y, and p.G633S) have also been reported in MFS patients, suggesting functional importance of this codon and nearby region. In addition, in an internal tested sample from a MFS patient, this variant has been confirmed as a de novo, further supporting a pathogenic outcome. Taken together, this variant is classified as likely pathogenic. |