Submissions for variant NM_000371.4(TTR):c.260G>A (p.Gly87Glu)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV004702059	SCV005201570	likely pathogenic	not provided	2024-03-05	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.(G67E); This variant is associated with the following publications: (PMID: 27859927, 31135236, 22320251, 17968690, 26656838)
Labcorp Genetics (formerly Invitae), Labcorp	RCV005103553	SCV005837809	likely pathogenic	Amyloidosis, hereditary systemic 1	2024-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 87 of the TTR protein (p.Gly87Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary transthyretin-mediated amyloidosis (PMID: 17968690, 19180884, 22320251, 26656838). This variant is also known as Gly67Glu. 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 expected to disrupt TTR protein function with a positive predictive value of 95%. This variant disrupts the p.Gly87 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22320251, 28802308). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.