Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003344150 | SCV004057907 | uncertain significance | Cardiovascular phenotype | 2023-07-15 | criteria provided, single submitter | clinical testing | The p.Y1310N variant (also known as c.3928T>A), located in coding exon 23 of the SOS1 gene, results from a T to A substitution at nucleotide position 3928. The tyrosine at codon 1310 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Pittsburgh Clinical Genomics Laboratory, |
RCV004784142 | SCV005397671 | uncertain significance | Noonan syndrome 4 | 2024-06-19 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (T>A) at position 3928 of the coding sequence of the SOS1 gene that results in a tyrosine to asparagine amino acid change at residue 1310 of the SOS Ras/Rac guanine nucleotide exchange factor 1 protein. This is a previously reported variant (ClinVar 2587629) that has not been observed in individuals affected by SOS1-related conditions in the published literature, to our knowledge. This variant is absent from the gnomAD V4.1.0 population database (0/~1613000). Multiple bioinformatic tools predict that this tyrosine to asparagine amino acid change would be damaging, and the Tyr1310 residue at this position is highly conserved across the vertebrate species examined. Studies examining the functional consequence of this variant have not been published, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: PM2, PP3 |