Submissions for variant NM_015450.3(POT1):c.1251del (p.Leu418fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003179278	SCV003866748	pathogenic	Hereditary cancer-predisposing syndrome	2022-12-20	criteria provided, single submitter	clinical testing	The c.1251delA pathogenic mutation, located in coding exon 10 of the POT1 gene, results from a deletion of one nucleotide at nucleotide position 1251, causing a translational frameshift with a predicted alternate stop codon (p.L418Yfs*17). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003746663	SCV004487017	pathogenic	Tumor predisposition syndrome 3	2023-01-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu418Tyrfs*17) in the POT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POT1 are known to be pathogenic (PMID: 32155570).