ClinVar Miner

Submissions for variant NM_005633.4(SOS1):c.109A>G (p.Thr37Ala)

gnomAD frequency: 0.00016  dbSNP: rs150565592
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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000159147 SCV000616432 likely benign RASopathy 2017-04-03 reviewed by expert panel curation The c.109A>G (p.Thr37Ala) variant did not segregate with disease in affected family members (BS4; Partners LMM internal data; GTR Lab ID: 21766; ClinVar SCV000062187.5). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; Partners LMM internal data; GTR Lab ID: 21766; ClinVar SCV000062187.5). Computational prediction tools and conservation analysis suggest that the p.Thr37Ala variant does not impact the protein (BP4). In summary, this variant meets criteria to be classified as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BS4, BP5, BP4.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038509 SCV000062187 benign not specified 2018-02-28 criteria provided, single submitter clinical testing p.Thr37Ala in exon 2 of SOS1: This variant is not expected to have clinical sig nificance because it has been identified in 0.026% (34/126670) of European chrom osomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute .org; dbSNP rs150565592). It was identified in one individual with clinical feat ures of Noonan syndrome who also carried a pathogenic variant in PTPN11. This va riant was also identified in that individual's unaffected parent. In addition, i n another family, it was identified in only one of two siblings with a clinical diagnosis of Noonan syndrome. ACMG/AMP Criteria applied: BS1, BS2, BP4, BP5.
GeneDx RCV001703446 SCV000209091 benign not provided 2019-01-08 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 23487764, 21387466)
Labcorp Genetics (formerly Invitae), Labcorp RCV000159147 SCV000218752 likely benign RASopathy 2024-01-10 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000038509 SCV000331385 likely benign not specified 2016-04-19 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001143267 SCV001303775 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina RCV001143269 SCV001303777 uncertain significance 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813278 SCV002060630 likely benign Noonan syndrome and Noonan-related syndrome 2020-01-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002453283 SCV002736080 likely benign Cardiovascular phenotype 2021-01-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001703446 SCV004564225 likely benign not provided 2023-06-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001703446 SCV004699433 likely benign not provided 2024-01-01 criteria provided, single submitter clinical testing SOS1: BP4
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001703446 SCV001957137 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001703446 SCV001970437 likely benign not provided no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003904889 SCV004718330 likely benign SOS1-related disorder 2020-08-27 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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