ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.1269C>G (p.Asn423Lys)

dbSNP: rs138459502
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159188 SCV000209134 uncertain significance not provided 2022-11-28 criteria provided, single submitter clinical testing Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 12628188, 21387466, 17143282, 29493581, 20648242)
Labcorp Genetics (formerly Invitae), Labcorp RCV000556655 SCV000659126 likely benign RASopathy 2023-02-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192794 SCV001361141 uncertain significance not specified 2019-08-05 criteria provided, single submitter clinical testing Variant summary: SOS1 c.1269C>G (p.Asn423Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250564 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.1269C>G in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002444456 SCV002682681 uncertain significance Cardiovascular phenotype 2024-05-12 criteria provided, single submitter clinical testing The p.N423K variant (also known as c.1269C>G), located in coding exon 10 of the SOS1 gene, results from a C to G substitution at nucleotide position 1269. The asparagine at codon 423 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV002467508 SCV002763446 uncertain significance Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467507 SCV002763447 uncertain significance Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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