Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000478350 | SCV000564960 | pathogenic | not provided | 2024-05-17 | criteria provided, single submitter | clinical testing | Has been reported in affected individuals segregating with disease in unrelated families with features of EFNB1-related craniofrontonasal dysplasia (PMID: 15124102, 31837199, 16685650); note this variant has been listed using alternate c. nomenclature (c.862C>T) in PMID: 15124102; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect (PMID: 20565770); This variant is associated with the following publications: (PMID: 18043713, 31837199, 15124102, 16685650, 20565770) |
| Department of Medical Genetics, |
RCV000012474 | SCV001437561 | likely pathogenic | Craniofrontonasal syndrome | criteria provided, single submitter | clinical testing | ||
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV000012474 | SCV002568250 | pathogenic | Craniofrontonasal syndrome | 2022-06-27 | criteria provided, single submitter | clinical testing | PS3, PS4_Supporting, PM1, PM2, PM5_Supporting, PP3 |
| Labcorp Genetics |
RCV000478350 | SCV003445081 | pathogenic | not provided | 2022-05-28 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 54 of the EFNB1 protein (p.Pro54Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with craniofrontonasal syndrome (PMID: 15124102, 16685650, 18043713, 31837199). It has also been observed to segregate with disease in related individuals. This variant is also known as 862C>T. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects EFNB1 function (PMID: 20565770). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 11708). |
| OMIM | RCV000012474 | SCV000032708 | pathogenic | Craniofrontonasal syndrome | 2004-06-01 | no assertion criteria provided | literature only |