ClinVar Miner

Submissions for variant NM_000371.4(TTR):c.223C>A (p.Leu75Met)

dbSNP: rs2073510448
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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 RCV001044452 SCV001208250 pathogenic Amyloidosis, hereditary systemic 1 2023-09-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu75 amino acid residue in TTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1351039, 12557757, 17503405, 21843040, 23713495, 26123280, 28272196). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 842099). This missense change has been observed in individual(s) with clinical features of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 75 of the TTR protein (p.Leu75Met).

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