Submissions for variant NM_000535.7(PMS2):c.1344A>T (p.Gly448=) (rs759192470)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164596	SCV000215255	likely benign	Hereditary cancer-predisposing syndrome	2014-12-09	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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	RCV000229726	SCV000285065	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2019-12-23	criteria provided, single submitter	clinical testing	This sequence change affects codon 448 of the PMS2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PMS2 protein. This variant is present in population databases (rs759192470, ExAC 0.001%) but has not been reported in the literature in individuals with a PMS2-related disease. ClinVar contains an entry for this variant (Variation ID: 185217). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000442013	SCV000517396	likely benign	not specified	2016-12-14	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.
Color	RCV000164596	SCV000911287	likely benign	Hereditary cancer-predisposing syndrome	2017-11-07	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000442013	SCV000920043	likely benign	not specified	2019-08-29	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000998766	SCV001155032	uncertain significance	not provided	2019-01-01	criteria provided, single submitter	clinical testing