Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000589150 | SCV000209086 | uncertain significance | not provided | 2017-12-04 | criteria provided, single submitter | clinical testing | The H1175P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The H1175P variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The H1175P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. However, the SOS1 gene is known to have a low rate of benign missense variation. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589150 | SCV000698636 | uncertain significance | not provided | 2017-02-27 | criteria provided, single submitter | clinical testing | Variant summary: The SOS1 c.3524A>C (p.His1175Pro) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant is absent in 119768 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
Labcorp Genetics |
RCV001230717 | SCV001403207 | likely benign | RASopathy | 2024-05-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002453288 | SCV002616030 | uncertain significance | Cardiovascular phenotype | 2019-06-11 | criteria provided, single submitter | clinical testing | The p.H1175P variant (also known as c.3524A>C), located in coding exon 23 of the SOS1 gene, results from an A to C substitution at nucleotide position 3524. The histidine at codon 1175 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV002467528 | SCV002763566 | uncertain significance | Noonan syndrome 4 | criteria provided, single submitter | clinical testing | ||
Genome- |
RCV002467527 | SCV002763567 | uncertain significance | Fibromatosis, gingival, 1 | criteria provided, single submitter | clinical testing | ||
Fulgent Genetics, |
RCV002477050 | SCV002780082 | uncertain significance | Fibromatosis, gingival, 1; Noonan syndrome 4 | 2021-10-01 | criteria provided, single submitter | clinical testing |