ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.2122G>A (p.Ala708Thr)

gnomAD frequency: 0.00280  dbSNP: rs140811086
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000206629 SCV000616435 benign RASopathy 2017-04-03 reviewed by expert panel curation The filtering allele frequency of the c.2122G>A (p.Ala708Thr) variant in the SOS1 gene is 5.13% for Latino chromosomes by the Exome Aggregation Consortium (633/11554 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).
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038529 SCV000062207 benign not specified 2009-08-13 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000224003 SCV000206740 benign not provided 2023-10-06 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000038529 SCV000225875 benign not specified 2015-04-21 criteria provided, single submitter clinical testing
Invitae RCV000206629 SCV000260509 benign RASopathy 2024-02-01 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224003 SCV000281177 benign not provided 2015-05-22 criteria provided, single submitter clinical testing
Preventiongenetics, part of Exact Sciences RCV000038529 SCV000311189 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001094653 SCV000430427 likely benign Noonan syndrome 4 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000272488 SCV000430428 likely benign Fibromatosis, gingival, 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852769 SCV000995488 benign Primary dilated cardiomyopathy; Cardiomyopathy; Hypertrophic cardiomyopathy 2019-05-28 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001258236 SCV001435142 benign Joubert syndrome 3 criteria provided, single submitter research The heterozygous p.Ala708Thr variant in SOS1 has only been previously reported in individuals without Noonan syndrome but has been reported in association with Noonan syndrome (PMID: 22585553, 21340158), and has been identified in >5% of Latino chromosomes and 23 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal dominant Noonan syndrome.
GeneDx RCV000224003 SCV001860109 benign not provided 2018-12-13 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27153395, 21387466, 27535533, 22585553, 21340158)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813293 SCV002060640 benign Noonan syndrome and Noonan-related syndrome 2021-04-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV002415454 SCV002729928 benign Cardiovascular phenotype 2018-06-01 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002496503 SCV002813134 benign Fibromatosis, gingival, 1; Noonan syndrome 4 2022-05-03 criteria provided, single submitter clinical testing

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