Laterality disorders and isomerism
Gene: CFC1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. The GMS stated there was not enough evidence yet to be green, and some of it is conflicting, and some evidence suggests a recurring variant may be a predispostion gene and not be completely causative. Should stay amberCreated: 31 Jan 2023, 1:07 p.m. | Last Modified: 31 Jan 2023, 1:07 p.m.
Panel Version: 2.3
This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.Created: 13 Apr 2021, 2:27 p.m. | Last Modified: 13 Apr 2021, 2:27 p.m.
Panel Version: 1.32
PMID: 31633655 - 1 patient with a heterozygous missense, paternally inherited. The proband has situs inversus with biliary atresia, while the father did not have biliary atresia but did have situs inversus
PMID: 18162845 - recurring missense (p.Ala145Thr) reported in 5 patients with biliary atresia splenic malformation syndrome. Authors conclude the variant may not be completely causative but create a predisposition to the syndrome. This variant has 145 hets in the population (gnomAD) but with strong strand bias - may not be real. Discount this piece of evidence.
PMID: 25423076 - 8 patients reported with heterotaxy and CNVs resulting in the deletion of CFC1. Clear breakpoints not mentioned, but CNVs may be multigenic. Piece of evidence not considered.
PMID: 11062482 - 9 heterozygous patients with mostly missense but also one PTC. Null zebrafish model recapitulate the mutant phenotype, could not be rescued by 2 mutant mRNA.
Some conflicting evidence, but overall enough for Green.Created: 1 Jun 2020, 9:01 a.m. | Last Modified: 1 Jun 2020, 9:01 a.m.
Panel Version: 1.5
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Heterotaxy, visceral, 2, autosomal 605376
Publications
not on CGGL Royal Brompton panel. Limited evidence in literatureCreated: 25 Nov 2019, 9:47 p.m. | Last Modified: 25 Nov 2019, 9:47 p.m.
Panel Version: 0.51
Phenotypes
OMIM 605376 Heterotaxy, visceral, 2, autosomal
Publications
Comment on list classification: Downgraded from Green to Amber after expert review. Change of rating will be included in update with Test Group to enable further comment/review if required before sign off.Created: 27 Nov 2019, 1:10 p.m. | Last Modified: 27 Nov 2019, 1:10 p.m.
Panel Version: 0.132
From Panel Familial non syndromic congenital heart disease. 4 Jul 2017, 7:24 a.m. Panel version: 1.8. Review by Helen Brittain (Genomics England Curator). Green List (high evidence). Comment on list classification: Sufficient evidence in relation to heterotaxy phenotype. Therefore promoted to green. Three (/?four) unrelated laterality cases with two LOF mutations in listed PMID. Considered sufficient cases for inclusion. Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown. Phenotypes: Heterotaxy, visceral, 2, autosomal, 605376; Visceral Heterotaxy, Heterotaxy, Visceral, 2, Autosomal. Publications: 11062482.Created: 17 Jan 2019, 1:55 p.m.
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: CFC1; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PCD or Visceral heterotaxy gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none givenCreated: 5 Dec 2018, 12:52 p.m.
Publications
Tag Q2_21_rating was removed from gene: CFC1. Tag Q2_21_expert_review was removed from gene: CFC1.
Tag Q2_21_expert_review tag was added to gene: CFC1.
Tag Q2_21_rating tag was added to gene: CFC1.
Phenotypes for gene: CFC1 were changed from Heterotaxy, visceral, 2, 605376 to Heterotaxy, visceral, 2, autosomal, OMIM:605376
Publications for gene: CFC1 were set to 11062482; 25423076
Gene: cfc1 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: CFC1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CFC1 were changed from to Heterotaxy, visceral, 2, 605376
Publications for gene: CFC1 were set to 11062482
Publications for gene: CFC1 were set to
Source Expert Review Green was added to CFC1. Rating Changed from Red List (low evidence) to Green List (high evidence)
gene: CFC1 was added gene: CFC1 was added to Laterality disorders and isomerism. Sources: NHS GMS Mode of inheritance for gene: CFC1 was set to