ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3709C>T (p.Pro1237Ser)

dbSNP: rs371408734
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001816259 SCV002063851 uncertain significance not provided 2021-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869642 SCV002163627 uncertain significance RASopathy 2022-11-01 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SOS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1335388). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is present in population databases (rs371408734, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1237 of the SOS1 protein (p.Pro1237Ser).
Ambry Genetics RCV002359268 SCV002625232 uncertain significance Cardiovascular phenotype 2022-01-03 criteria provided, single submitter clinical testing The p.P1237S variant (also known as c.3709C>T), located in coding exon 23 of the SOS1 gene, results from a C to T substitution at nucleotide position 3709. The proline at codon 1237 is replaced by serine, an amino acid with 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.
Genome-Nilou Lab RCV002468326 SCV002763551 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468325 SCV002763552 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003407819 SCV004113518 uncertain significance SOS1-related disorder 2023-06-01 criteria provided, single submitter clinical testing The SOS1 c.3709C>T variant is predicted to result in the amino acid substitution p.Pro1237Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-39213258-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.