ClinVar Miner

Submissions for variant NM_001142730.3(KCTD1):c.2056G>C (p.Asp686His)

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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 RCV004594860 SCV005086729 likely pathogenic Scalp-ear-nipple syndrome 2023-12-21 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established (PMIDs: 23541344, 31324836). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Scalp-ear-nipple syndrome exhibits substantial variable expressivity within families (PMID: 23541344). (I) 0200 - Variant is predicted to result in a missense amino acid change from aspartic acid to histidine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and high conservation. (I) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants. The affected amino acid residue has been annotated as a pentamer interface region within the BTB_2 domain (DECIPHER, NCBI). The majority of the reported missense variants in this gene are also located in the same region (PMID: 23541344). Five of those missense variants have been shown to impair the ability to bind to AP-2 alpha (PMID: 31324836). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis performed by an external laboratory). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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