ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.720T>C (p.Asn240=)

dbSNP: rs779699814
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Total submissions: 4
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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 RCV004767426 SCV000698644 uncertain significance not specified 2024-08-12 criteria provided, single submitter clinical testing Variant summary: SOS1 c.720T>C (p.Asn240Asn) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.720T>C has been reported in the literature in individuals in the context of Noonan Syndrome And Related Conditions (Leach_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Noonan Syndrome And Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29907801). ClinVar contains an entry for this variant (Variation ID: 496311). Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860140 SCV002316620 uncertain significance RASopathy 2024-01-20 criteria provided, single submitter clinical testing This sequence change affects codon 240 of the SOS1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SOS1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs779699814, gnomAD 0.003%). This variant has been observed in individual(s) with clinical features of noonan syndrome and related conditions (PMID: 29907801). ClinVar contains an entry for this variant (Variation ID: 496311). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Genome-Nilou Lab RCV002467914 SCV002763511 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467913 SCV002763512 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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