ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1202+3G>A

gnomAD frequency: 0.00001  dbSNP: rs904487658
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192792 SCV001361138 uncertain significance not specified 2019-01-07 criteria provided, single submitter clinical testing Variant summary: SOS1 c.1202+3G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 274746 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1202+3G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002348639 SCV002651204 uncertain significance Cardiovascular phenotype 2021-12-14 criteria provided, single submitter clinical testing The c.1202+3G>A intronic variant results from a G to A substitution 3 nucleotides after coding exon 9 in the SOS1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002468186 SCV002763457 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002468185 SCV002763458 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002560156 SCV003447836 uncertain significance RASopathy 2022-05-21 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 928619). 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. This variant has not been reported in the literature in individuals affected with SOS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 of the SOS1 gene. It does not directly change the encoded amino acid sequence of the SOS1 protein. It affects a nucleotide within the consensus splice site.

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