Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000234075 | SCV001424750 | likely benign | RASopathy | 2020-06-25 | reviewed by expert panel | curation | The c.3322G>A (p.Asp1108Asn) variant in SOS1 was present in 0.039% (10/13658 with 95% CI) of Latino alleles in gnomAD v3 (BS1). This variant has been identified in a patient with Noonan syndrome who had an alternate molecular basis for disease (BP5; SCV000966758.1; ClinVar ID: 44603). It was also identified in a homozygous state in an individual who also carried a variant in TRMT1 (BP5 not met; Baylor College of Medicine internal data). In summary, this variant meets criteria to be classified as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BS1, BP5. |
Labcorp Genetics |
RCV000234075 | SCV000288965 | uncertain significance | RASopathy | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1108 of the SOS1 protein (p.Asp1108Asn). This variant is present in population databases (rs199856844, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Noonan spectrum disorders (Invitae). ClinVar contains an entry for this variant (Variation ID: 240197). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SOS1 protein function. 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. |
Gene |
RCV000333119 | SCV000330895 | likely benign | not provided | 2021-03-22 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000825457 | SCV000966758 | uncertain significance | not specified | 2018-05-02 | criteria provided, single submitter | clinical testing | The p.Asp1108Asn variant has not been previously reported in individuals with cl inical features of a RASopathy disorder, but has been reported in ClinVar (Varia tion ID: 238770). This variant has been identified in 4/33558 Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; d bSNP rs199856844). Please note that for diseases with clinical variability, redu ced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and co nservation analysis suggest that the p.Asp1108Asn variant may not impact the pro tein, though this information is not predictive enough to rule out pathogenicity . In summary, the clinical significance of the p.Asp1108Asn variant is uncertain . ACMG/AMP Criteria applied: BP4. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000825457 | SCV002103791 | uncertain significance | not specified | 2022-02-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002321878 | SCV002606225 | likely benign | Cardiovascular phenotype | 2024-10-03 | 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. |