Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001064985 | SCV001229923 | pathogenic | not provided | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1691 of the FLNB protein (p.Gly1691Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant Larsen syndrome or atelosteogenesis III (PMID: 14991055, 16648377, 16752402, 27048506). In at least one individual the variant was observed to be de novo. This variant is also known as p.Gly1722Ser. ClinVar contains an entry for this variant (Variation ID: 6406). 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 not expected to disrupt FLNB protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000030663 | SCV000026971 | pathogenic | Larsen syndrome | 2007-02-01 | no assertion criteria provided | literature only | |
Gene |
RCV000030663 | SCV000040872 | not provided | Larsen syndrome | no assertion provided | literature only | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001064985 | SCV001951181 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001064985 | SCV001966721 | pathogenic | not provided | no assertion criteria provided | clinical testing |