Submissions for variant NM_024675.4(PALB2):c.2368C>T (p.Gln790Ter)

dbSNP: rs886039480

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255054	SCV000322103	likely pathogenic	not provided	2017-11-20	criteria provided, single submitter	clinical testing	This variant is denoted PALB2 c.2368C>T at the cDNA level and p.Gln790Ter (Q790X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered likely pathogenic.
Ambry Genetics	RCV000454204	SCV000538151	pathogenic	Hereditary cancer-predisposing syndrome	2023-06-12	criteria provided, single submitter	clinical testing	The p.Q790* pathogenic mutation (also known as c.2368C>T), located in coding exon 5 of the PALB2 gene, results from a C to T substitution at nucleotide position 2368. This changes the amino acid from a glutamine to a stop codon within coding exon 5. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000255054	SCV000601758	likely pathogenic	not provided	2017-05-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552634	SCV000633346	pathogenic	Familial cancer of breast	2023-11-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln790*) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 265329). RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000255054	SCV001449539	pathogenic	not provided	2019-09-19	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000552634	SCV004175486	pathogenic	Familial cancer of breast	2023-07-12	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000552634	SCV004188549	pathogenic	Familial cancer of breast	2023-09-12	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Baylor Genetics	RCV000552634	SCV004202767	pathogenic	Familial cancer of breast	2021-12-08	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV000255054	SCV005197080	pathogenic	not provided	2022-05-27	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000509375	SCV000607177	not provided	Fanconi anemia; Hereditary cancer		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
BRCAlab, Lund University	RCV003155937	SCV002588997	pathogenic	Hereditary breast ovarian cancer syndrome	2022-08-26	no assertion criteria provided	clinical testing