Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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, |
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. |
Gene |
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 |
RCV000159147 | SCV000218752 | likely benign | RASopathy | 2024-01-10 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000038509 | SCV000331385 | likely benign | not specified | 2016-04-19 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
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, |
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, |
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, |
RCV001703446 | SCV004564225 | likely benign | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | |
Ce |
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, |
RCV001703446 | SCV001957137 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001703446 | SCV001970437 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Prevention |
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). |