ClinVar Miner

Submissions for variant NM_005912.3(MC4R):c.690del (p.Gly231fs)

dbSNP: rs758387065
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521516 SCV000621596 uncertain significance not provided 2017-10-10 criteria provided, single submitter clinical testing The c.690delC variant in the MC4R gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.690delC variant causes a frameshift starting with codon Glycine 231, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 11 of the new reading frame, denoted p.Gly231AlafsX11. This variant is predicted to cause loss of normal protein function through protein truncation. The c.690delC variant is observed in 4/33578 (0.012%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016). We interpret c.690delC as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000521516 SCV002996372 uncertain significance not provided 2022-02-04 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. ClinVar contains an entry for this variant (Variation ID: 452764). This variant has not been reported in the literature in individuals affected with MC4R-related conditions. This variant is present in population databases (rs758387065, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Gly231Alafs*11) in the MC4R gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 102 amino acid(s) of the MC4R protein.
PreventionGenetics, part of Exact Sciences RCV004748809 SCV005348693 pathogenic MC4R-related disorder 2023-12-24 no assertion criteria provided clinical testing The MC4R c.690delC variant is predicted to result in a frameshift and premature protein termination (p.Gly231Alafs*11). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD. Frameshift variants in MC4R are expected to be pathogenic. This variant is interpreted as pathogenic.

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