ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.103C>T (p.Pro35Ser) (rs397514590)

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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 RCV000033008 SCV000266524 pathogenic Shprintzen-Goldberg syndrome criteria provided, single submitter research
Baylor Genetics RCV000033008 SCV000807264 uncertain significance Shprintzen-Goldberg syndrome 2017-09-01 criteria provided, single submitter clinical testing This variant has been previously reported as disease-causing and was found once in our laboratory de novo in a 3-year-old female with global delays, hypotonia, dysmorphisms, craniosynostosis, hypermobile joints, abnormal reflexes, short stature, hydrocephalus, hydronephrosis, scoliosis, talipes equinovarus
Invitae RCV000033008 SCV000816608 pathogenic Shprintzen-Goldberg syndrome 2018-02-09 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 35 of the SKI protein (p.Pro35Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to be de novo in individuals affected with Shprintzen-Goldberg syndrome (PMID: 23023332, 23103230, 24736733, 24357594). ClinVar contains an entry for this variant (Variation ID: 39786). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Pro35Gln) has been reported as de novo in an individual affected with Shprintzen-Goldberg syndrome (PMID: 23103230). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000033008 SCV000056787 pathogenic Shprintzen-Goldberg syndrome 2015-02-01 no assertion criteria provided literature only

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