Submissions for variant NM_000371.4(TTR):c.259G>C (p.Gly87Arg)

dbSNP: rs11541799

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001303075	SCV001492309	likely pathogenic	Familial amyloid neuropathy	2022-11-29	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. This variant disrupts the p.Gly87 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in individuals with TTR-related conditions (PMID: 17968690, 22320251), which suggests that this may be a clinically significant amino acid residue. 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 TTR protein function. ClinVar contains an entry for this variant (Variation ID: 1006084). This variant is also known as Gly67Arg. This missense change has been observed in individual(s) with familial transthyretin amyloidosis (PMID: 28802308). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 87 of the TTR protein (p.Gly87Arg).
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV001303075	SCV001571578	uncertain significance	Familial amyloid neuropathy	2020-12-02	no assertion criteria provided	clinical testing