ClinVar Miner

Submissions for variant NM_006939.4(SOS2):c.3735T>G (p.Asp1245Glu)

gnomAD frequency: 0.00002  dbSNP: rs752525400
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001947466 SCV002133855 likely benign Noonan syndrome 9 2024-01-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282622 SCV002570829 uncertain significance not specified 2022-07-11 criteria provided, single submitter clinical testing Variant summary: SOS2 c.3735T>G (p.Asp1245Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251462 control chromosomes (gnomAD). 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.3735T>G in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: it was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV001947466 SCV002762980 uncertain significance Noonan syndrome 9 criteria provided, single submitter clinical testing
Ambry Genetics RCV003375391 SCV004096329 uncertain significance Cardiovascular phenotype 2023-08-11 criteria provided, single submitter clinical testing The p.D1245E variant (also known as c.3735T>G), located in coding exon 23 of the SOS2 gene, results from a T to G substitution at nucleotide position 3735. The aspartic acid at codon 1245 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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