Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV003460857 | SCV004205331 | uncertain significance | PMS1-related breast cancer | 2023-09-28 | criteria provided, single submitter | clinical testing | |
ITMI | RCV000121832 | SCV000086030 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Department of Pathology and Laboratory Medicine, |
RCV001355189 | SCV001549999 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PMS1 p.Arg630* variant was identified in the literature in a female patient with uveal melanoma, congenital bilateral nevus of Ota and ocular surface melanosis (Toomey_2019_PMID:31367589). The variant was identified in dbSNP (ID: rs139932286) and ClinVar (submitted by ITMI, classification not provided). The variant was identified in control databases in 38 of 266820 chromosomes at a frequency of 0.0001424 (Genome Aggregation Database March 6, 2019, v2.1.1, non-cancer). The variant was observed in the following populations: Ashkenazi Jewish in 22 of 9822 chromosomes (freq: 0.00224), Latino in 5 of 35036 chromosomes (freq: 0.000143), South Asian in 3 of 30488 chromosomes (freq: 0.000098) and European (non-Finnish) in 8 of 117296 chromosomes (freq: 0.000068), but was not observed in the African, East Asian, European (Finnish), or Other populations. The c.1888C>T variant leads to a premature stop codon at position 630 which is predicted to lead to a truncated or absent protein and loss of function. However, the role of loss of function PMS1 variants in disease is not currently well established. The variant occurs 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. This variant is classified as a variant of uncertain significance. |