Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000231032 | SCV000289888 | uncertain significance | CHARGE association | 2019-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 619 of the SEMA3E protein (p.Arg619Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs143631464, ExAC 0.02%). This variant has been reported in two brothers with Kallmann syndrome (PMID: 25985275) and an individual with CHARGE syndrome, who inherited the variant from an unaffected parent (PMID: 15235037). ClinVar contains an entry for this variant (Variation ID: 221681). Experimental studies have shown that this missense change disrupts the ability of the protein to prevent cell death in cultured neurons (PMID: 25985275). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000207418 | SCV000262695 | uncertain significance | not provided | 2016-02-09 | no assertion criteria provided | literature only |