Submissions for variant NM_014694.4(ADAMTSL2):c.1321G>A (p.Glu441Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002472222	SCV002769317	uncertain significance	Geleophysic dysplasia 1	2020-05-25	criteria provided, single submitter	clinical testing	A heterozygous missense variant was identified, NM_001145320.1(ADAMTSL2):c.1321G>A in exon 11 of the ADAMTSL2 gene. This substitution is predicted to create a minor amino acid change from a glutamic acid to a lysine at position 441 of the protein; NP_001138792.1(ADAMTSL2):p.(Glu441Lys). The glutamic acid at this position has low conservation (100 vertebrates, UCSC), and is not situated in a known functional domain (NCBI, PDB). In silico software predicts this variant to be tolerated (PolyPhen2, PROVEAN, FATHMM, Mutation Assessor). The variant is not present in the gnomAD population database, however this region of gnomAD has no coverage. This variant has not previously been reported in clinical cases. Based on information available at the time of curation, this variant has been classified as a VUS with LOW CLINICAL RELEVANCE.
GeneDx	RCV004817037	SCV005439394	uncertain significance	not provided	2024-06-21	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge