ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.100G>T (p.Gly34Cys) (rs387907306)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University RCV000030820 SCV000266522 pathogenic Shprintzen-Goldberg syndrome criteria provided, single submitter research
Invitae RCV000030820 SCV000637271 pathogenic Shprintzen-Goldberg syndrome 2017-06-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 34 of the SKI protein (p.Gly34Cys). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and cysteine. While this variant is not present in population databases (rs387907306), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been shown to arise de novo in individuals affected with Shprintzen-Goldberg syndrome (PMID: 23023332, 23103230). ClinVar contains an entry for this variant (Variation ID: 37262). Several different missense substitutions at this codon (p.Gly34Asp, p.Gly34Ser, p.Gly34Val) have been determined to be pathogenic (PMID: 23023332, 23103230, 24736733). This suggests that the glycine residue is critical for SKI protein function and that other missense substitutions at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000623016 SCV000743082 pathogenic Inborn genetic diseases 2017-11-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
OMIM RCV000030820 SCV000053495 pathogenic Shprintzen-Goldberg syndrome 2012-11-02 no assertion criteria provided literature only

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