ClinVar Miner

Submissions for variant NM_004586.3(RPS6KA3):c.1686dup (p.Gly563fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004594749 SCV005086224 pathogenic Coffin-Lowry syndrome 2024-09-20 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Coffin-Lowry syndrome (MIM#303600) and intellectual developmental disorder, X-linked 19 (MIM#300844). (I) 0110 - This gene is associated with X-linked dominant disease. Females may be severely affected or very mild, with some affected males having inherited their variants from unaffected mothers (PMID: 19888300, PMID: 16879200). (I) 0115 - Variants in this gene are known to have variable expressivity, with intrafamilial variability reported (PMID: 32858545). (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. Many NMD-predicted variants have previously been reported as pathogenic (DECIPHER). (SP) 0803 - This variant has limited previous evidence of pathogenicity in an unrelated individual. This variant has been reported in an individual with Coffin-Lowry syndrome (PMID: 16879200). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1101 - Very strong and specific phenotype match for this individual. (SP) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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