ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.1230G>A (p.Gln410=) (rs141390073)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000203903 SCV000616438 benign Rasopathy 2017-04-03 reviewed by expert panel curation The c.1230G>A (p.Gln410=) variant in SOS1 has been identified in a patient with an alternate molecular basis for disease (BP5; Partners LMM internal data GTR Lab ID: 21766 ClinVar SCV000062189.5). This variant is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). Computational prediction tools and conservation analysis suggest that the p.Gln410= variant does not impact the protein (BP4). The filtering allele frequency of the c.1230G>A (p.Gln410=) variant in the SOS1 gene is 4.69% for Latino chromosomes by the Exome Aggregation Consortium (580/11526 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). In summary, this variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5, BP7, BP4.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038511 SCV000062189 benign not specified 2010-05-07 criteria provided, single submitter clinical testing Changed to benign since variant has been observed in two individuals with other known pathogenic variants in PTPN11.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000038511 SCV000224969 benign not specified 2014-09-17 criteria provided, single submitter clinical testing
Invitae RCV000203903 SCV000259254 benign Rasopathy 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000038511 SCV000311184 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001094607 SCV000430437 benign Noonan syndrome 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000336293 SCV000430438 benign Gingival fibromatosis 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000038511 SCV001156861 benign not specified 2018-09-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000156987 SCV000206710 benign Noonan syndrome 2014-05-29 no assertion criteria provided clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000157704 SCV000207693 uncertain significance not provided 2015-01-15 no assertion criteria provided clinical testing

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