Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213087 | SCV000275387 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-08-14 | criteria provided, single submitter | clinical testing | The p.S104* pathogenic mutation (also known as c.311C>G), located in coding exon 3 of the APC gene, results from a C to G substitution at nucleotide position 311. This changes the amino acid from a serine to a stop codon within coding exon 3. This mutation has been detected in multiple individuals with a personal and/or family history of polyposis (Garzón-Benavides M et al. Rev Esp Enferm Dig, 2010 Nov;102:653-7; Ambry internal data). In a cohort of 300 deceased patients who underwent whole genome sequencing for 60 autosomal dominant cancer predisposition genes, this variant was detected and classified as likely pathogenic by the authors. However, the specific phenotype of the patient with this alteration was not reported (He KY et al. PLoS One, 2016 Dec;11:e0167847). In addition to the clinical data presented in the literature, 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. |
| ARUP Laboratories, |
RCV000506152 | SCV000602536 | pathogenic | not specified | 2017-03-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000519665 | SCV000617331 | likely pathogenic | not provided | 2017-03-10 | criteria provided, single submitter | clinical testing | This variant is denoted APC c.311C>G at the cDNA level and p.Ser104Ter (S104X) at the protein level. The substitution creates a nonsense variant, which changes a Serine to a premature stop codon (TCA>TGA). While this variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay, Heppner Gross (2002) has demonstrated the production of a functional truncated APC protein, although at a low level, through the use of an alternate downstream Methionine codon. This variant has been reported in at least one individual with a personal and/or family history suggestive of Familial Adenomatous Polyposis (Garzon-Benavides 2010). Based on the currently available information, we consider this variant to be likely pathogenic. |
| Institute Of Human Genetics Munich, |
RCV001254064 | SCV001429974 | pathogenic | Familial adenomatous polyposis 1 | 2017-10-18 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003335254 | SCV002232943 | pathogenic | Familial adenomatous polyposis 1 | 2023-11-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser104*) in the APC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APC are known to be pathogenic (PMID: 17963004, 20685668). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 21142386). ClinVar contains an entry for this variant (Variation ID: 231513). For these reasons, this variant has been classified as Pathogenic. |
| Myriad Genetics, |
RCV003335254 | SCV004044782 | pathogenic | Familial adenomatous polyposis 1 | 2023-04-25 | 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 | RCV001254064 | SCV004207339 | pathogenic | Familial adenomatous polyposis 1 | 2022-11-14 | criteria provided, single submitter | clinical testing |