rs746118995

Positions:

chr19-11120143-C-T

Variant summary

Our verdict is Pathogenic. Variant got 20 ACMG points: 20P and 0B. PS1_ModeratePM1PM2PM5PP3_StrongPP5_Very_Strong

The NM_000527.5(LDLR):c.1897C>T(p.Arg633Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R633H) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

LDLR
NM_000527.5 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:27

Conservation

PhyloP100: 1.45

Variant links:

Genes affected

LDLR (HGNC:6547): (low density lipoprotein receptor) The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2022]

LDLR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 20 ACMG points.

PS1

Transcript NM_000527.5 (LDLR) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM1

In a turn (size 2) in uniprot entity LDLR_HUMAN there are 9 pathogenic changes around while only 0 benign (100%) in NM_000527.5

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr19-11120144-G-A is described in Lovd as [Pathogenic].

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

PP5

Variant 19-11120143-C-T is Pathogenic according to our data. Variant chr19-11120143-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 226379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11120143-C-T is described in Lovd as [Pathogenic]. Variant chr19-11120143-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLR	NM_000527.5 linkuse as main transcript	c.1897C>T	p.Arg633Cys	missense_variant	13/18	ENST00000558518.6	NP_000518.1	P01130-1A0A024R7D5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLR	ENST00000558518.6 linkuse as main transcript	c.1897C>T	p.Arg633Cys	missense_variant	13/18	1	NM_000527.5	ENSP00000454071.1		P01130-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251490

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000351

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:27

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypercholesterolemia, familial, 1

Pathogenic:17

Likely pathogenic, criteria provided, single submitter	research	Fundacion Hipercolesterolemia Familiar	Mar 01, 2016	- -
Pathogenic, no assertion criteria provided	clinical testing	Cardiovascular Genetics Laboratory, PathWest Laboratory Medicine WA - Fiona Stanley Hospital	Jan 09, 2015	- -
Pathogenic, criteria provided, single submitter	clinical testing	U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	Mar 30, 2017	- -
Pathogenic, no assertion criteria provided	research	Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	-	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation	Nov 05, 2016	- -
Pathogenic, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Aug 05, 2024	This missense variant (also known as p.Arg612Cys in the mature protein) replaces arginine with cysteine at codon 633 in the LDLR type B repeat 6 of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study using transfected LDLR-deficient CHO-ldlA7 cells has shown that this variant causes a significant reduction in LDLR expression and activity (PMID: 32015373). This variant has been reported in over 10 individuals affected with familial hypercholesterolemia (PMID: 9259195, 15241806, 16159606, 17094996, 17539906, 19446849, 19843101, 20538126, 22698793, 23375686, 27765764, 28028493, 28235710, 31491741). This variant has also been observed in compound heterozygous and homozygous state in individuals affected with homozygous familial hypercholesterolemia (PMID: 17094996, 19538517, 27784735), indicating that this variant contributes to disease. This variant has been identified in 3/251490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Arg633His, is considered to be disease-causing (ClinVar variation ID: 226380), suggesting that arginine at this position is important for LDLR protein function. Based on the available evidence, this variant is classified as Pathogenic. -
Likely pathogenic, criteria provided, single submitter	research	Laboratory of Genetics and Molecular Cardiology, University of São Paulo	Mar 01, 2016	- -
Pathogenic, criteria provided, single submitter	clinical testing	Neuberg Centre For Genomic Medicine, NCGM	-	NA -
Pathogenic, criteria provided, single submitter	clinical testing	Juno Genomics, Hangzhou Juno Genomics, Inc	-	PM2_Supporting+PS3_Moderate+PS4+PP4+PM3 -
Pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Aug 02, 2022	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	Jan 14, 2018	The c.1897C>T (p.Arg633Cys) variant in the LDLR gene has been reported in several unrelated individuals with familial hypercholesterolemia (PMID: 9259195, 15241806, 19446849, 19843101, 21376320, 22698793, 23375686). Moreover, two other variants at the same residue (p.Arg633His, and p.Arg633Leu) have also been described in multiple individuals with familial hypercholesterolemia (PMID: 16250003, 22390909) suggesting that the Arg633 residue is critical for normal functioning of the LDLR protein. In light of the currently available data this variant in the LDLR gene is classified likely pathogenic -
Likely pathogenic, criteria provided, single submitter	clinical testing	Robarts Research Institute, Western University	-	- -
Pathogenic, criteria provided, single submitter	clinical testing	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	Oct 11, 2022	PS3, PM1, PM2, PM5, PP1 -
Pathogenic, no assertion criteria provided	clinical testing	Clinical Genomics Laboratory, Stanford Medicine	Sep 23, 2021	The p.Arg633Cys variant in the LDLR gene has been reported in at least 10 unrelated individuals with familial hypercholesterolemia (Day et al., 1997; Mozas et al., 2004; Graham et al., 2005; Tosi et al., 2007; Guardamagna et al., 2009; Tichý et al., 2012; Hori et al., 2019; Xiang et al., 2019). Additionally, this variant was found in the compound heterozygous state with a multi-exon deletion in an individual with suspected homozygous familial hypercholesterolemia (Taylor et al., 2009). This variant is also referred to as R612C in the literature. Notably, two different amino acid changes (p.Arg633Leu, p.Arg633His) at this residue have been previously reported in multiple unrelated individuals. This variant has been identified in 3/251,490 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with the prevalence of familial hypercholesterolemia. A functional study of p.Arg633Cys showed reduced LDLR expression and reduced LDL binding activity, supporting a deleterious effect to the protein (Galicia-Garcia et al., 2020). Computational tools predict that this variant is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the p.Arg633Cys variant as pathogenic for autosomal dominant familial hypercholesterolemia based on the information above. [ACMG evidence codes used: PS4; PM2; PM3; PS3_Supporting; PP3] -
Pathogenic, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 28, 2017	The LDLR c.1897C>T (p.Arg633Cys) variant has been reported in at least eight studies and is found in a total of at least 11 individuals with familial hypercholesterolemia, including one who carried the variant in a compound heterozygous state along with a deletion and in a heterozygous state in ten individuals (Day et al. 1997; Mozas et al. 2004; Taylor et al. 2007; Guardamagna et al. 2009; Taylor et al. 2009; Chiou et al. 2010; TichÃ½ et al. 2012; Bertolini et al. 2013). The p.Arg633Cys variant was absent from 100 controls, and is not found in the 1000 Genomes Project, the Exome Sequencing Project, or the Exome Aggregation Consortium, in a region of good sequence coverage, and hence is presumed to be rare. Based on the evidence, the p.Arg633Cys variant is classified as pathogenic for familial hypercholesterolemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
Pathogenic, criteria provided, single submitter	clinical testing	Arcensus	Feb 01, 2013	- -
Likely pathogenic, criteria provided, single submitter	literature only	LDLR-LOVD, British Heart Foundation	Mar 25, 2016	- -

Familial hypercholesterolemia

Pathogenic:5

Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 633 of the LDLR protein (p.Arg633Cys). This variant is present in population databases (rs746118995, gnomAD 0.003%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 9259195, 15241806, 19446849, 19538517, 19843101, 21376320, 22698793, 23375686). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as p.Arg612Cys. ClinVar contains an entry for this variant (Variation ID: 226379). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	-	This variant is also referred to as p.Arg612Cys in the literature. This variant has been reported as a heterozygous change in individuals with features of familial hypercholesterolemia (PMID: 28349888, 27680772, 9259195, 15241806, 27578128, 21376320, 28235710). Functional studies have shown that the c.1897C>T (p.Arg633Cys) variant results in abnormal function of the LDLR protein (PMID: 32015373). The c.1897C>T (p.Arg633Cys) variant is present in the heterozygous state in the gnomAD population database at a frequency of 0.001% (3/251490). It affects a moderately conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Different missense variants involving the same residue (p.Arg633His and p.Arg633Leu) have been previously reported in individuals with familial hypercholesterolemia (ClinVar Variation ID: 226380, 252107). Based on the available evidence, the c.1897C>T (p.Arg633Cys) variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Nov 08, 2016	Variant summary: The LDLR c.1897C>T (p.Arg633Cys) variant, alternatively also known as R612C, is located in EGF precursor homology domain of the LDLR protein (Mozas_2004, Bertolini_2013) and 4/4 in silico tools predict a damaging outcome for this substitution. This variant is absent in 121614 control chromosomes including broad and large populations from ExAC. In literature, this variant is widely reported as a pathogenic variant and is found in several FH patients. Other missense variants in this codon, p.Arg633Leu and p.Arg633His, have been reported as FH patients and are classified as pathogenic/likely pathogenic in ClinVar, suggesting that the codon p.Arg633 is mutational hot-spot. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Apr 27, 2023	This missense variant (also known as p.Arg612Cys in the mature protein) replaces arginine with cysteine at codon 633 in the LDLR type B repeat 6 of the LDLR protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). A functional study using transfected LDLR-deficient CHO-ldlA7 cells has shown that this variant causes a significant reduction in LDLR expression and activity (PMID: 32015373). This variant has been reported in over 10 individuals affected with familial hypercholesterolemia (PMID: 9259195, 15241806, 16159606, 17094996, 17539906, 19446849, 19843101, 20538126, 22698793, 23375686, 27765764, 28028493, 28235710, 31491741). This variant has also been observed in compound heterozygous and homozygous state in individuals affected with homozygous familial hypercholesterolemia (PMID: 17094996, 19538517, 27784735), indicating that this variant contributes to disease. This variant has been identified in 3/251490 chromosomes in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, p.Arg633His, is considered to be disease-causing (ClinVar variation ID: 226380), suggesting that arginine at this position is important for LDLR protein function. Based on the available evidence, this variant is classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	Aug 01, 2023	The c.1897C>T (p.Arg633Cys) variant in the LDLR gene is located on the exon 13 and is predicted to replace arginine with cysteine at codon 633 (p.Arg633Cys). The variant has been identified in more than 10 unrelated individuals with familial hypercholesterolemia (FH) (PMID: 27680772, 28235710, 28349888, 31893465, 21376320, 22698793, 15241806, 17094996). Other variants disrupting the same amino acid (p.Arg633Leu, p.Arg633His) have been interpreted as likely pathogenic (ClinVar ID: 252107, 226380). The variant is rare in the general population according to gnomAD (3/251490). Computational prediction algorithms suggest a deleterious impact for this variant (REVEL score 0.845). Therefore, the c.1897C>T (p.Arg633Cys) variant of LDLR has been classified as pathogenic. -

not provided

Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jan 26, 2022	Not observed at a 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 suggest a damaging effect as Western blotting showed decreased expression and reduced LDL uptake suggesting a negative effect on LDLR receptor recycling (Galicia-Garcia et al., 2020); Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#226379; ClinVar); Also reported as R612C due to alternate nomenclature; This variant is associated with the following publications: (PMID: 28349888, 27680772, 9259195, 15241806, 27578128, 28235710, 19843101, 16159606, 20538126, 23375686, 19446849, 18700895, 17539906, 22698793, 21376320, 19538517, 17094996, 32015373, 31447099, 31491741, 30586733, 31589614, 34037665, 33087929, 32041611, 32719484) -
Pathogenic, criteria provided, single submitter	clinical testing	AiLife Diagnostics, AiLife Diagnostics	Feb 21, 2022	- -

Homozygous familial hypercholesterolemia

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 04, 2019

The p.Arg633Cys variant in LDLR has been reported in at least 11 individuals with familial hypercholesterolemia (FH), including one homozygote (Day 1997, Mozas 2004, Guardamagna 2009, Taylor 2009, Chiou 2011, Tichy 2012, Bertolini 2013, Xiang 2017, Medieros 2017). This variant has been reported in ClinVar (Variation ID: 226379) and has also been identified in 1/30782 South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the p.Arg833Cys variant may impact the protein. Two other variants at this amino acid position have been reported in at least 4 individuals with FH (p.Arg633Leu and p.Arg633His). In summary, although additional studies are required to fully establish its clinical significance, the p.Arg633Cys variant is likely pathogenic. ACMG/AMP Criteria applied: PS4_Moderate, PM2, PM5_Supporting, PP3. -

LDLR-related disorder

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 22, 2024

The LDLR c.1897C>T variant is predicted to result in the amino acid substitution p.Arg633Cys. This variant (also reported as c.Arg612Cys in the literature) has been reported in many unrelated individuals with familial hypercholesterolemia (Mozas et al. 2004. PubMed ID: 15241806; Chiou et al. 2011. PubMed ID: 21376320; Tichý et al. 2012. PubMed ID: 22698793; Day et al. 1997. PubMed ID: 9259195, referred to as R612C; Bertolini et al. 2013. PubMed ID: 23375686, supplementary data; Di Taranto et al. 2019. PubMed ID: 30710474, supplementary data; Dron et al. 2020. PubMed ID: 32041611; Sturm et al. 2021. PubMed ID: 34037665, supplementary data; Futema et al. 2017. PubMed ID: 28349888). In vitro analysis of this variant indicated that this variant results in diminished LDLR expression and activity (Galicia-Garcia et al. 2020. PubMed ID: 32015373). This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD. This variant has been reported in ClinVar by many outside laboratories as likely pathogenic or pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/226379/). Two other amino acid substitutions at this position (p.Arg633His and p.Arg633Leu) have also been reported in individuals with hypercholesterolemia (Fouchier et al. 2005. PubMed ID: 16250003; Di Taranto et al. 2021. PubMed ID: 34297352). In summary, we categorize c.1897C>T (p.Arg633Cys) as pathogenic. -

Cardiovascular phenotype

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 03, 2024

The c.1897C>T (p.R633C) alteration is located in exon 13 (coding exon 13) of the LDLR gene. This alteration results from a C to T substitution at nucleotide position 1897, causing the arginine (R) at amino acid position 633 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (3/251490) total alleles studied. The highest observed frequency was 0.003% (1/30616) of South Asian alleles. This variant (also known as p.R612C) has been reported in numerous individuals and cohorts with familial hypercholesterolemia (FH) (Day, 1997; Sánchez-Hernández, 2016; Wang, 2016). Alternate amino acid substitutions at this codon, p.R633L and p.R633H, have also been reported in individuals with FH (Fouchier, 2005). Based on the available evidence, this alteration is classified as pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.48

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.96

D;.;.;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

M;.;.;.;.;M

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.0

D;D;D;D;D;D

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.99

D;.;.;.;.;.

Vest4

0.67

MutPred

0.96

Gain of catalytic residue at L634 (P = 0.0077);Gain of catalytic residue at L634 (P = 0.0077);.;.;.;Gain of catalytic residue at L634 (P = 0.0077);

MVP

1.0

MPC

0.95

ClinPred

0.95

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 10

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over