Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000487385 | SCV000568824 | uncertain significance | not provided | 2016-11-29 | criteria provided, single submitter | clinical testing | The c.599_604dupGGGCCC variant in the POMC gene has been reported previously, according to alternate nomeclature, in cis with a nonsense variant (E206X) and in trans with a missense variant (E214G), in a German adolescent female with obesity (Hinney et al., 1998). The c.599_604dupGGGCCC variant results in an in-frame insertion of two residues, an Arginine and an Alanine, at position 202 in the protein, denoted p.Ala201_Gln202insArgAla. The c.599_604dupGGGCCC variant was not observed with any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, we interpret c.599_604dupGGGCCC as a variant of uncertain significance. |
New York Genome Center | RCV001263288 | SCV001441327 | uncertain significance | Obesity; Abnormality of skin pigmentation | 2019-05-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000487385 | SCV002213309 | uncertain significance | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This variant, c.599_604dup, results in the insertion of 2 amino acid(s) of the POMC protein (p.Ala201_Gln202insArgAla), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs762710034, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has been observed in individual(s) with obesity, in cis with a nearby nonsense variant (PMID: 9768693, 29970488, 35574020). ClinVar contains an entry for this variant (Variation ID: 420163). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |