Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000214931 | SCV000278144 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-05-22 | criteria provided, single submitter | clinical testing | The c.3524C>G (p.T1175S) alteration is located in exon 6 (coding exon 6) of the MSH6 gene. This alteration results from a C to G substitution at nucleotide position 3524, causing the threonine (T) at amino acid position 1175 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Gene |
RCV000486443 | SCV000566053 | uncertain significance | not provided | 2015-03-25 | criteria provided, single submitter | clinical testing | This variant is denoted MSH6 c.3524C>G at the cDNA level, p.Thr1175Ser (T1175S) at the protein level, and results in the change of a Threonine to a Serine (ACT>AGT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Thr1175Ser was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Threonine and Serine share similar properties, this is considered a conservative amino acid substitution. MSH6 Thr1175Ser occurs at a position that is conserved across species and is located in domain V of the MutS domain (Terui 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH6 Thr1175Ser is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Mendelics | RCV000708890 | SCV000837917 | uncertain significance | Lynch syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001066026 | SCV001231019 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1175 of the MSH6 protein (p.Thr1175Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 233711). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MSH6 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Color Diagnostics, |
RCV000214931 | SCV001353079 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-11-02 | criteria provided, single submitter | clinical testing |