Submissions for variant NM_015450.3(POT1):c.1682del (p.Asp561fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002609539	SCV002967795	pathogenic	Tumor predisposition syndrome 3	2022-01-23	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 present in population databases (rs765028767, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Asp561Valfs*14) 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).
Ambry Genetics	RCV003348874	SCV004058324	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-11	criteria provided, single submitter	clinical testing	The c.1682delA pathogenic mutation, located in coding exon 13 of the POT1 gene, results from a deletion of one nucleotide at nucleotide position 1682, causing a translational frameshift with a predicted alternate stop codon (p.D561Vfs*14). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with POT1-related disease (Ambry internal data). 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.