ClinVar Miner

Submissions for variant NM_018848.3(MKKS):c.830T>C (p.Leu277Pro) (rs74315398)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000481638 SCV000229154 uncertain significance not provided 2015-01-21 criteria provided, single submitter clinical testing
GeneDx RCV000481638 SCV000568396 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing The L277P variant in the MKKS gene has been reported previously in two unrelated individuals with Bardet-Biedl syndrome who each also harbored a loss-of-function variant in MKKS (Katsanis et al., 2000; Moore et al., 2005). The L277P variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L277P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. Functional studies demostrated that L277P could not rescue the morphant phenotype in zebrafish embryos, suggesting that L277P has a damaging effect on the MKKS protein (Zaghloul et al., 2010). We interpret L277P as a pathogenic variant.
Gharavi Laboratory,Columbia University RCV000481638 SCV000809233 likely pathogenic not provided 2018-09-16 no assertion criteria provided research
OMIM RCV000005639 SCV000025821 pathogenic Bardet-Biedl syndrome 6 2005-02-01 no assertion criteria provided literature only

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