ClinVar Miner

Submissions for variant NM_000371.4(TTR):c.311T>A (p.Ile104Asn)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003516383 SCV004297828 pathogenic Amyloidosis, hereditary systemic 1 2022-12-20 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 104 of the TTR protein (p.Ile104Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with amyloidosis (PMID: 1350083). This variant is also known as p.Ile84Asn. 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. This variant disrupts the p.Ile104 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2840822, 3760189, 9547003, 9701270, 17503405, 23713495, 25997029). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

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