Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CSER _CC_NCGL, |
RCV000148776 | SCV000190513 | uncertain significance | Medullary thyroid carcinoma | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
Invitae | RCV000231209 | SCV000290569 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2019-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 321 of the RET protein (p.Gly321Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs377767388, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in a family affected with medullary thyroid carcinoma and/or C-cell hyperplasia. However, the variant did not segregate with disease in this family (PMID: 16419493). ClinVar contains an entry for this variant (Variation ID: 24881). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
Ambry Genetics | RCV000567555 | SCV000674744 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-09 | criteria provided, single submitter | clinical testing | Insufficient evidence |
Prevention |
RCV000679758 | SCV000807066 | uncertain significance | not provided | 2018-01-17 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000709104 | SCV000838373 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Research and Development, |
RCV000021762 | SCV000042428 | uncertain significance | not specified | 2018-05-04 | no assertion criteria provided | literature only | Single Czech family report, 4 have the variant genotype: 1 metastatic MTC (61 yr), 1 bi-lateral C-cell hyperplasia (42 yr). |