Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165970 | SCV000216727 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-06-21 | criteria provided, single submitter | clinical testing | The c.597_599delTGC variant (also known as p.A199del) is located in coding exon 5 of the FH gene. This variant results from an in-frame deletion of 3 nucleotides (TGC) at positions 597 to 599, causing the removal of a highly-conserved alanine residue at codon 199. This variant has been detected in multiple individuals who meet clinical diagnostic criteria for HLRCC (Ambry internal data). In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Invitae | RCV002515155 | SCV000819344 | uncertain significance | not provided | 2022-08-16 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 186384). This variant has been observed in individual(s) with clinical features of FH-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This variant, c.597_599del, results in the deletion of 1 amino acid(s) of the FH protein (p.Ala200del), but otherwise preserves the integrity of the reading frame. |