Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000307912 | SCV000341751 | uncertain significance | not provided | 2016-06-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001079080 | SCV001001244 | likely benign | RASopathy | 2024-01-15 | criteria provided, single submitter | clinical testing | |
St. |
RCV001775112 | SCV002012430 | uncertain significance | Noonan syndrome | 2021-10-12 | criteria provided, single submitter | clinical testing | The SOS1 c.3387C>T (p.Gly1129=) synonymous change has a maximum subpopulation frequency of 0.0070% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/2-39216415-G-A?dataset=gnomad_r2_1). This frequency does not meet criteria for PM2 or BS1 as defined by the RASopathy Variant Curation Expert Panel (PMID:29493581). Algorithms that predict the impact of sequence changes on splicing indicate that this variant does not affect splicing (BP4). RNA data demonstrates skipping of exon 21 in approximately 30% of reads (internal data), however the functional significance of this consequence is currently unknown. To our knowledge, this variant has not been reported in individuals with Noonan syndrome. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria, as specified by the RASopathy Variant Curation Expert Panel (PMID:29493581): BP4. |
Ambry Genetics | RCV002450823 | SCV002616230 | likely benign | Cardiovascular phenotype | 2019-11-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |