Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000756859 | SCV000209362 | likely benign | not provided | 2020-12-08 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21406045, 30683924, 32376792) |
| Invitae | RCV000697928 | SCV000826562 | uncertain significance | Familial amyloid neuropathy | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 119 of the TTR protein (p.Asp119Asn). This variant is present in population databases (rs76410435, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of TTR-related conditions (PMID: 32376792, 34658264; Invitae). This variant is also known as D99N. ClinVar contains an entry for this variant (Variation ID: 181690). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect TTR function (PMID: 21406045). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| ARUP Laboratories, |
RCV000756859 | SCV000884816 | likely benign | not provided | 2017-12-20 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000697928 | SCV001283900 | likely benign | Familial amyloid neuropathy | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Molecular Genetics Laboratory, |
RCV001173299 | SCV001336383 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
| Ambry Genetics | RCV002336372 | SCV002618826 | likely benign | Cardiovascular phenotype | 2020-01-23 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |