Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673122 | SCV000798290 | likely pathogenic | Fanconi anemia complementation group C | 2018-03-07 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001021633 | SCV001183273 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.3G>T) is located in coding exon 1 of the FANCC gene and results from a G to T substitution at nucleotide position 3. This alters the methionine residue at the initiation codon (ATG). Although there is an alternate in-frame methionine 16 amino acids downstream from the initiation site, alterations truncating the protein between p.M1 and p.M16 are identified in many patients with Fanconi Anemia (Chandrasekharappa SC et al. Blood, 2013 May;121:e138-48; Steinberg-Shemer O et al. Haematologica, 2020 07;105:1825-1834; Murer-Orlando M et al. Lancet, 1993 Sep;342:686; Verlander PC et al. Am J Hum Genet, 1994 Apr;54:595-601; Gillio AP et al. Blood, 1997 Jul;90:105-10; Nicchia E et al. Mol Genet Genomic Med, 2015 Nov;3:500-12). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |