ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.345+12_345+13dup

gnomAD frequency: 0.00050  dbSNP: rs397517167
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038551 SCV000062229 likely benign not specified 2012-09-18 criteria provided, single submitter clinical testing 345+12_345+13dupCT in intron 3 of SOS1: This variant is not expected to be clini cal significant because it is not located in the conserved region of the splicin g consensus sequence.
GeneDx RCV000159122 SCV000209066 benign RASopathy 2014-04-07 criteria provided, single submitter clinical testing The variant is found in NOONAN,CARDIOMYOPATHY panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038551 SCV001361403 benign not specified 2019-12-09 criteria provided, single submitter clinical testing Variant summary: SOS1 c.345+12_345+13dupCT alters a non-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 allele was found at a frequency of 0.00046 in 250972 control chromosomes, predominantly at a frequency of 0.00087 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 29 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome and Related Conditions phenotype (3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, 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 benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000159122 SCV002408380 benign RASopathy 2024-01-21 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467552 SCV002763591 benign Noonan syndrome 4 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV002467551 SCV002763592 benign Fibromatosis, gingival, 1 criteria provided, single submitter clinical testing

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