Submissions for variant NM_001457.4(FLNB):c.5072G>A (p.Gly1691Asp)

dbSNP: rs1553704446

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000625945	SCV000746536	likely pathogenic	Larsen syndrome	2020-05-03	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814201	SCV001755563	likely pathogenic	Abnormality of the skeletal system	2021-07-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860468	SCV002243776	pathogenic	not provided	2024-09-24	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1691 of the FLNB protein (p.Gly1691Asp). 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 (PMID: 22190451; internal data). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 522782). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt FLNB protein function with a negative predictive value of 95%. This variant disrupts the p.Gly1691 amino acid residue in FLNB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14991055, 16648377, 16752402, 27048506). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.