Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000888138 | SCV001031752 | likely benign | not provided | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000888138 | SCV001249021 | uncertain significance | not provided | 2019-07-01 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000888138 | SCV001551986 | likely benign | not provided | no assertion criteria provided | clinical testing | The ERBB3 p.Leu1177Ile variant was identified in the literature in a colorectal tumor with multiple other variants identified (Silverstein_2019_PMID:31370007). The variant was identified in dbSNP (ID: rs55699040) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 673 of 282866 chromosomes (2 homozygous) at a frequency of 0.002379 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 569 of 129182 chromosomes (freq: 0.004405), Other in 19 of 7228 chromosomes (freq: 0.002629), Ashkenazi Jewish in 12 of 10370 chromosomes (freq: 0.001157), Latino in 37 of 35438 chromosomes (freq: 0.001044), African in 23 of 24960 chromosomes (freq: 0.000922), European (Finnish) in 11 of 25118 chromosomes (freq: 0.000438) and South Asian in 2 of 30616 chromosomes (freq: 0.000065), but was not observed in the East Asian population. The p.Leu1177 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. The variant occurs outside of the splicing consensus sequence and 1 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |