Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000899962 | SCV001044258 | likely benign | not provided | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003950544 | SCV004761571 | likely benign | ROBO3-related condition | 2022-01-24 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Department of Pathology and Laboratory Medicine, |
RCV000899962 | SCV001550731 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The ROBO3 p.Thr613Ile variant was not identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs200202857) and in control databases in 206 of 280618 chromosomes (1 homozygous) at a frequency of 0.000734 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 192 of 24190 chromosomes (freq: 0.007937), Latino in 13 of 35366 chromosomes (freq: 0.000368) and Other in 1 of 7140 chromosomes (freq: 0.00014), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), and South Asian populations. The T613I variant was identified in a family with hypoplastic Amelogenesis Imperfecta however it was not considered to be damaging (Acevedo_2015_PMID:25928877). The p.Thr613 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. 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. |