Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019187 | SCV001180515 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-07-17 | criteria provided, single submitter | clinical testing | The p.H311Q variant (also known as c.933C>G), located in coding exon 9 of the PMS2 gene, results from a C to G substitution at nucleotide position 933. The histidine at codon 311 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Department of Pathology and Laboratory Medicine, |
RCV001356846 | SCV001552117 | uncertain significance | Carcinoma of colon | no assertion criteria provided | clinical testing | The PMS2 p.His311Gln variant was not identified in the literature nor was it identified in the dbSNP or ClinVar databases. The variant was not identified in the following control databases: the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.His311 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 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. |