ClinVar Miner

Submissions for variant NM_002107.7(H3-3A):c.362T>C (p.Met121Thr)

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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 RCV004788222 SCV005398703 pathogenic Bryant-Li-Bhoj neurodevelopmental syndrome 1 2022-02-02 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: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Affected individuals displayed varying degrees of developmental delay (PMID: 33268356). (I) 0200 - Variant is predicted to result in a missense amino acid change from methionine to threonine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2: 1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0602 - Variant is located in a hotspot region or cluster of pathogenic variants (PMID: 33268356). (SP) 0703 - Other missense variants comparable to the one identified in this case have moderate previous evidence for pathogenicity. p.(Met121Lys) and p.(Met121Ile) have been reported de novo in two individuals with progressive neurologic dysfunction and congenital anomalies (PMID: 33268356). (SP) 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). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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