Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131596 | SCV000186610 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-21 | criteria provided, single submitter | clinical testing | The p.A70V variant (also known as c.209C>T), located in coding exon 1 of the MSH2 gene, results from a C to T substitution at nucleotide position 209. The alanine at codon 70 is replaced by valine, an amino acid with similar properties. This amino acid position is well 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. |
Invitae | RCV000805430 | SCV000945386 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-09-24 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 142464). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 70 of the MSH2 protein (p.Ala70Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. |
Genetics and Molecular Pathology, |
RCV002466443 | SCV002761705 | likely pathogenic | Lynch syndrome 1 | 2021-08-23 | criteria provided, single submitter | clinical testing | |
Genetics and Molecular Pathology, |
RCV002466444 | SCV002761756 | likely pathogenic | Lynch syndrome | 2020-04-03 | criteria provided, single submitter | clinical testing |