Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000463473 | SCV000553277 | likely benign | RASopathy | 2023-12-18 | criteria provided, single submitter | clinical testing | |
Phosphorus, |
RCV000577966 | SCV000679915 | uncertain significance | Noonan syndrome 4 | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000592644 | SCV000709736 | uncertain significance | not specified | 2018-03-06 | criteria provided, single submitter | clinical testing | Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 7/121778 Europeans in gnomad-2:39214706 A / T, identified in 1 individual with possible Noonan syndrome, but classified as a VUS Lepri et al., 2011, benign by prediction tools |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000592644 | SCV001363486 | likely benign | not specified | 2024-07-02 | criteria provided, single submitter | clinical testing | Variant summary: SOS1 c.3418T>A (p.Leu1140Ile) results in a conservative amino acid change located in the SH3-binding motifs (Lepri_2011) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 1589486 control chromosomes. The observed variant frequency is approximately 5.35 fold of the estimated maximal expected allele frequency for a pathogenic variant in SOS1 causing Noonan Syndrome And Related Conditions phenotype (3e-05). c.3418T>A has been reported in the literature in individuals affected with Noonan Syndrome and Related Conditions (Lepri_2011, Ceyhan-Birsoy_2018, Shapiro_2017). Some of these report(s) classify the variant as a VUS and overall, do not provide unequivocal conclusions about association of the variant with Noonan Syndrome And Related Conditions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 29696744, 21387466, 28870985). ClinVar contains an entry for this variant (Variation ID: 40729). Based on the evidence outlined above, the variant was classified as likely benign. |
Gene |
RCV001588841 | SCV001825022 | likely benign | not provided | 2019-06-06 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21387466) |
Ambry Genetics | RCV002453287 | SCV002614312 | likely benign | Cardiovascular phenotype | 2023-12-04 | 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. |