Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000212638 | SCV000170349 | benign | not specified | 2014-02-14 | 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. |
Ambry Genetics | RCV000126823 | SCV000213111 | likely benign | Hereditary cancer-predisposing syndrome | 2014-06-24 | 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. |
Invitae | RCV001081374 | SCV000252632 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000409252 | SCV000488839 | likely benign | Lynch syndrome 5 | 2016-06-29 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000212638 | SCV000595846 | likely benign | not specified | 2017-04-17 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000126823 | SCV000685532 | benign | Hereditary cancer-predisposing syndrome | 2015-09-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588033 | SCV000695936 | benign | not provided | 2016-01-04 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000212638 | SCV000706960 | likely benign | not specified | 2017-04-28 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000212638 | SCV000889513 | benign | not specified | 2021-07-21 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000212638 | SCV001158617 | benign | not specified | 2019-06-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000409252 | SCV001302621 | likely benign | Lynch syndrome 5 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Sema4, |
RCV000126823 | SCV002536377 | likely benign | Hereditary cancer-predisposing syndrome | 2021-06-14 | criteria provided, single submitter | curation | |
KCCC/NGS Laboratory, |
RCV000409252 | SCV004015998 | benign | Lynch syndrome 5 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000409252 | SCV004018986 | benign | Lynch syndrome 5 | 2023-03-29 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Ce |
RCV000588033 | SCV004033729 | likely benign | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | MSH6: BP4, BP7 |
CHEO Genetics Diagnostic Laboratory, |
RCV003492570 | SCV004239330 | likely benign | Breast and/or ovarian cancer | 2023-01-17 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997441 | SCV004837536 | benign | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355092 | SCV001549867 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The MSH6 p.Ser328Ser= variant was not identified in the literature. The variant was identified in dbSNP (rs138143769) as “with uncertain significance, other allele”, ClinVar (classified as benign by Invitae, GeneDx, Color and 3 other submitters; and as likely benign by Ambry Genetics, Eurofins, Counsyl and 1 other submitter) and UMD-LSDB (observed 1x). The variant was identified in control databases in 81 of 282,780 chromosomes (1 homozygous) at a frequency of 0.0003 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 72 of 24,954 chromosomes (freq: 0.003, increasing the likelihood this could be a low frequency benign variant), Latino in 5 of 35,436 chromosomes (freq: 0.0001), and European in 4 of 129,118 chromosomes (freq: 0.00003), while it was not observed in the Ashkenazi Jewish, East Asian, Finnish, Other, or South Asian populations. The p.Ser328= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |