ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.3763C>A (p.Pro1255Thr)

gnomAD frequency: 0.00001  dbSNP: rs972166211
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000475839 SCV000553273 uncertain significance RASopathy 2024-01-03 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1255 of the SOS1 protein (p.Pro1255Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SOS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 411867). 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 with a negative predictive value of 95%. 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000593291 SCV000709739 uncertain significance not specified 2018-03-01 criteria provided, single submitter clinical testing Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Not present in GnomAd-2:39213204 G / T- good coverage; Not in Google search or HGMD; VUS in ClinVar by Invitae
GeneDx RCV001755704 SCV001986988 uncertain significance not provided 2023-03-07 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29493581)
Genome-Nilou Lab RCV002467821 SCV002763537 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467820 SCV002763539 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002496789 SCV002781412 uncertain significance Fibromatosis, gingival, 1; Noonan syndrome 4 2021-07-23 criteria provided, single submitter clinical testing

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