ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3437A>G (p.Tyr1146Cys)

dbSNP: rs1750918319
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001332073 SCV001524275 uncertain significance Congenital contractural arachnodactyly 2019-05-17 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001332073 SCV003439196 likely pathogenic Congenital contractural arachnodactyly 2022-09-20 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN2 protein function. ClinVar contains an entry for this variant (Variation ID: 1030504). This missense change has been observed in individuals with clinical features of FBN2-related conditions (PMID: 19006240, 33895855; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1146 of the FBN2 protein (p.Tyr1146Cys).
CeGaT Center for Human Genetics Tuebingen RCV004597985 SCV005092148 likely pathogenic not provided 2024-07-01 criteria provided, single submitter clinical testing FBN2: PM2, PS4:Moderate, PP3, PP4
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004597985 SCV005197906 likely pathogenic not provided 2022-05-27 criteria provided, single submitter clinical testing

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