Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002547618 | SCV003010852 | likely benign | 46,XY sex reversal 6 | 2023-11-03 | criteria provided, single submitter | clinical testing | |
| Department of Pathology and Laboratory Medicine, |
RCV001355824 | SCV001550822 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The MAP3K1 p.Arg339Trp variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs373572109) and in control databases in 4 of 249332 chromosomes at a frequency of 0.000016 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 15486 chromosomes (freq: 0.000129), European (Finnish) in 1 of 21558 chromosomes (freq: 0.000046) and European (non-Finnish) in 1 of 113094 chromosomes (freq: 0.000009), but not in the Latino, Ashkenazi Jewish, East Asian, Other, and South Asian populations. The p.Arg339 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the R variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |