ClinVar Miner

Submissions for variant NM_005633.3(SOS1):c.109A>G (p.Thr37Ala) (rs150565592)

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Total submissions: 7
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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, Partners HealthCare 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 RCV000038509 SCV000209091 likely benign not specified 2015-11-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000159147 SCV000218752 likely benign Rasopathy 2019-08-25 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000038509 SCV000331385 likely benign not specified 2016-04-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001143267 SCV001303775 benign Gingival fibromatosis 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 Clinical Services Laboratory,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.

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