Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001430908 | SCV001633656 | likely benign | Multiple endocrine neoplasia, type 2 | 2024-03-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001732182 | SCV001983656 | benign | not specified | 2021-09-02 | criteria provided, single submitter | clinical testing | Variant summary: RET c.960C>T alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 3e-05 in 361586 control chromosomes, predominantly at a frequency of 0.00023 within the Latino subpopulation in the gnomAD database (v2.1 exomes-, and v3.1 genomes datasets). The observed variant frequency within Latino control individuals in the gnomAD database is approximately 6-fold of the estimated maximal expected allele frequency for a pathogenic variant in RET causing Multiple Endocrine Neoplasia Type 2 phenotype (3.7e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.960C>T in individuals affected with Multiple Endocrine Neoplasia Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |
| Ambry Genetics | RCV002384644 | SCV002695706 | benign | Hereditary cancer-predisposing syndrome | 2021-09-29 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
| Fulgent Genetics, |
RCV002504708 | SCV002806339 | likely benign | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A | 2021-10-17 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV001430908 | SCV005430312 | likely benign | Multiple endocrine neoplasia, type 2 | 2024-07-29 | criteria provided, single submitter | clinical testing |