rs140342925

Variant names:

Variant summary

Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PM5PP3_ModeratePP5_Very_Strong

The NM_001048174.2(MUTYH):c.650G>A(p.Arg217His) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,614,008 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R217L) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

MUTYH
NM_001048174.2 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:28O:1

Conservation

PhyloP100: 7.14

Variant links:

Genes affected

MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]

MUTYH links:

ENSG00000288208 (HGNC:):

ENSG00000288208 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 16 ACMG points.

PM1

In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 16 uncertain in NM_001048174.2

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-45332446-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 41761.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.889

PP5

Variant 1-45332445-C-T is Pathogenic according to our data. Variant chr1-45332445-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 140877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45332445-C-T is described in Lovd as [Pathogenic]. Variant chr1-45332445-C-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUTYH	NM_001048174.2 link	c.650G>A	p.Arg217His	missense_variant	Exon 9 of 16	ENST00000456914.7	NP_001041639.1	Q9UIF7-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUTYH	ENST00000456914.7 link	c.650G>A	p.Arg217His	missense_variant	Exon 9 of 16	1	NM_001048174.2	ENSP00000407590.2		Q9UIF7-6
ENSG00000288208	ENST00000671898.1 link	n.1238G>A		non_coding_transcript_exon_variant	Exon 13 of 21			ENSP00000499896.1		A0A5F9ZGZ0

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000839

AC:

AN:

250298

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000581

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000660

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000647

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000109

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:28Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial adenomatous polyposis 2

Pathogenic:9Other:1

Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Mar 25, 2024	- -
Pathogenic, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 11, 2019	The p.Arg245His variant in MUTYH has been reported in 1 homozygous individual, 2 heterozygous individuals, and 10 compound heterozygous individuals with MUTYH-related tumors (Aceto 2005, Olschwang 2007, Russell 2006, Vogt 2009, Win 2014, Yurgelun 2015). It segregated with disease in 3 affected relatives from 2 families (Vogt 2009). It has also been identified in 0.03% (5/19802) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This frequency is low enough to be consistent with the carrier frequency of MUTYH-related attenuated familial adenomatous polyposis (FAP) in the general population. This variant has been reported in ClinVar (Variation ID: 140877). Functional studies provide some evidence that the p.Arg245His variant has impaired function in vitro (Ali 2008, Ruggieri 2013, Grasso 2014, Komine 2015). In summary, this variant meets criteria to be classified as pathogenic for MUTYH-related attenuated FAP in an autosomal recessive manner. ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PS3_Moderate. -
Likely pathogenic, criteria provided, single submitter	clinical testing	Counsyl	Mar 31, 2016	- -
Pathogenic, criteria provided, single submitter	clinical testing	Revvity Omics, Revvity	Apr 19, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 07, 2017	Variant summary: The MUTYH c.734G>A (p.Arg245His) variant causes a missense change involving the alteration of a conserved nucleotide located in the DNA glycosylase domain and the Helix-turn-helix, base-excision DNA repair, C-terminal domain of the protein (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional assays showed the variant to be associated with defective glycosylase and DNA binding activity and concluded that this variant is functionally defective (Ali_2008, Komine_2015).The variant was found in the control population dataset of ExAC in 16/119648 control chromosomes at a frequency of 0.0001337, which does not exceed the estimated maximal expected allele frequency of a pathogenic MUTYH variant (0.0045644). This variant has been reported in numerous MUTYH-associated polyposis patients, in both homozygotes and compound heterozygotes (Aceto_2005, Vogt_2009). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 02, 2025	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 245 of the MUTYH protein (p.Arg245His). This variant is present in population databases (rs140342925, gnomAD 0.03%). This missense change has been observed in individual(s) with familial adenomatous polyposis and colorectal cancer (PMID: 16134147, 16557584, 19732775, 23108399, 24444654, 26446593). 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 c.692G>A (p.Arg231His). ClinVar contains an entry for this variant (Variation ID: 140877). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MUTYH function (PMID: 17081686, 18534194, 23108399, 24569162, 25820570). For these reasons, this variant has been classified as Pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Centre for Mendelian Genomics, University Medical Centre Ljubljana	May 27, 2019	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PM5,PP3. -
Pathogenic, criteria provided, single submitter	clinical testing	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	Apr 02, 2020	- -
not provided, no classification provided	phenotyping only	GenomeConnect - Invitae Patient Insights Network	-	Variant interpreted as Pathogenic and reported on 11-25-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. -
Pathogenic, criteria provided, single submitter	clinical testing	All of Us Research Program, National Institutes of Health	Jul 29, 2024	This missense variant replaces arginine with histidine at codon 245 of the MUTYH protein. This variant is also known by an alternative transcript, NM_001048171, as c.692G>A (p.Arg231His). A different variant affecting the same codon, c.733C>T (p.Arg245Cys), is considered to be disease-causing (ClinVar variation ID: 41761). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies found this variant to be defective in glycosylase assays (PMID: 18534194, 23108399) and caused abnormal increase in DNA 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and mutation frequency (PMID: 23108399, 24569162). This variant has been reported in multiple individuals who are heterozygous and homozygous carriers and affected with polyposis and colorectal cancer (PMID: 16134147,19394335, 19732775, 23108399, 25590978, 29406563, 29967336, 34704405). This variant has been identified in 24/281670 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -

not provided

Pathogenic:7

Likely pathogenic, criteria provided, single submitter	clinical testing	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	Nov 03, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2022	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as Arg231His; This variant is associated with the following publications: (PMID: 16134147, 16287072, 23108399, 24569162, 19732775, 24444654, 25980754, 26694661, 16557584, 28087410, 18534194, 25820570, 17949294, 16455870, 17081686, 26446593, 28551381, 27783336, 27870730, 27829682, 28152038, 26556299, 31159747, 30604180, 30564557, 29625052, 31263571, 29406563, 34426522, 31589614, 32338768, 30787465, 11801590) -
Pathogenic, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	Nov 19, 2021	The variant has been reported as homozygous or compound heterozygous in multiple individuals with MAP in the published literature (PMID: 23108399 (2013), 19732775 (2009), 16557584 (2006), 16134147 (2005)). Experimental studies indicate the variant is damaging to MUTYH protein function (PMID: 24569162 (2014), 23108399 (2013), 18534194 (2008)). Based on the available information, this variant is classified as pathogenic. -
Pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics and Genomics, Karolinska University Hospital	Mar 09, 2017	- -
Pathogenic, criteria provided, single submitter	clinical testing	Clinical Genetics Laboratory, Skane University Hospital Lund	May 27, 2022	- -
Pathogenic, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	MUTYH: PS3:Very Strong, PS4, PP3 -
Likely pathogenic, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Mar 04, 2025	- -

Hereditary cancer-predisposing syndrome

Pathogenic:5

Pathogenic, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 20, 2023	This missense variant replaces arginine with histidine at codon 245 of the MUTYH protein. This variant is also known by an alternative transcript, NM_001048171, as c.692G>A (p.Arg231His). A different variant affecting the same codon, c.733C>T (p.Arg245Cys), is considered to be disease-causing (ClinVar variation ID: 41761). Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies found this variant to be defective in glycosylase assays (PMID: 18534194, 23108399) and caused abnormal increase in DNA 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and mutation frequency (PMID: 23108399, 24569162). This variant has been reported in multiple individuals who are heterozygous and homozygous carriers and affected with polyposis and colorectal cancer (PMID: 16134147,19394335, 19732775, 23108399, 25590978, 29406563, 29967336, 34704405). This variant has been identified in 24/281670 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. -
Likely pathogenic, criteria provided, single submitter	clinical testing	GeneKor MSA	Jan 01, 2020	This variant is a missense mutation replacing Arginine with Histidine in the position 245 of the MUTYH protein. This particular Arginine is highly conserved and located in a functional domain of the protein (FeS cluster domain). However there is no significant physicochemical difference between Arginine and Histidine (Grantham Score 29). The aforementioned variant has been described in literature both in homozygosity and heterozygosity in patients with MUTYH-associated polyposis (PMID: 17949294 , PMID: 16287072, PMID: 16134147). Furthermore published functional studies have shown that the variant affects MUTYH protein functionality (PMID: 18534194, PMID: 23108399).This mutation is present at low frequency in population databases (rs140342925, 0.01%). The mutation database ClinVar contains an entry for this variant (Variation ID: 140877). -
Pathogenic, criteria provided, single submitter	clinical testing	Ambry Genetics	Nov 19, 2024	The p.R245H pathogenic mutation (also known as c.734G>A), located in coding exon 9 of the MUTYH gene, results from a G to A substitution at nucleotide position 734. The arginine at codon 245 is replaced by histidine, an amino acid with highly similar properties. This alteration has been reported in both the homozygous and compound heterozygous state in multiple individuals with colon polyposis and/or colorectal cancer (Aceto G et al. Hum. Mut. 2005 Oct;26:394; Russell AM et al. Int. J. Cancer. 2006 Apr;118:1937-40; Piccioli P et al. Clin. Chem. 2006 Apr;52:739-43; Olschwang S et al. Genet. Test. 2007;11:315-20; Jones N et al. Gastroenterology. 2009 Aug;137:489-94, 494.e1; quiz 725-6; Vogt S et al. Gastroenterology. 2009 Dec;137:1975-85; Morak M et al. Clin Genet, 2010 Oct;78:353-63; Win AK et al. Gastroenterology. 2014 May;146:1208-11.e1-5; Papp J et al. Fam. Cancer. 2016 Jan;15:85-97; Kacerovska D et al. Am. J. Dermatopathol. 2016 Dec;38:915-92; Ricci MT et al. J Hum Genet, 2017 Feb;62:309-315; Viel A et al. EBioMedicine, 2017 Jun;20:39-49; Yanus GA et al. Clin. Genet. 2018 May;93:1015-1021; Sutcliffe EG et al. Fam Cancer, 2019 04;18:203-209; Staninova-Stojovska M et al. Balkan J Med Genet, 2019 Dec;22:5-16). Functional studies have shown that the p.R245H mutation, which exists in the highly conserved and catalytic domain of MUTYH, results in severely defective glycosylase activity, severely defective DNA binding activity, and protein expression levels roughly half of that compared to wild-type (Ali M et al. Gastroenterology. 2008 Aug;135:499–507; Komine K et al. Hum. Mutat. 2015 Jul;36:704-11). Of note, this alteration is also designated as p.R231H (c.692G>A) in published literature. Based on the available evidence to date, this alteration is classified as a pathogenic mutation. -
Pathogenic, criteria provided, single submitter	curation	Sema4, Sema4	May 19, 2021	- -
Pathogenic, criteria provided, single submitter	clinical testing	Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	Mar 12, 2024	- -

Breast carcinoma

Pathogenic:2

Likely pathogenic, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Jan 01, 2019	- -
Likely pathogenic, no assertion criteria provided	clinical testing	Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	Aug 21, 2021	Invasive Breast Carcinoma EST= + PRO = - HER2 = - KI = 60-70% -

Carcinoma of colon

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The MUTYH p.Arg245His variant was identified in 15 (2 homozygous, remainder were compound heterozygous) of 3360 proband chromosomes (frequency: 0.004) from individuals or families with MUTYH-associated adenomatous polyposis, familial adenomatous polyposis, or Lynch syndrome and was present in 1 of 2440 control chromosomes (frequency: 0.0004) from healthy individuals (Ruggieri 2013, Vogt 2009, Aceto 2005, Russell 2006, Yanus 2018, Yurgelun 2015). The variant was also identified in dbSNP (ID: rs140342925) as "With Pathogenic allele", ClinVar (classified as pathogenic by Invitae, Ambry Genetics, GeneDx and three other submitters; and classified as likely pathogenic by three submitters), COGR, and UMD-LSDB (23x as causal variant; co-occurring with multiple pathogenic MUTYH mutations). The variant was not identified in Cosmic or MutDB. The variant was identified in control databases in 22 of 276400 chromosomes at a frequency of 0.00008 (Genome Aggregation Database Feb 27, 2017). The variant was identified in the following populations: East Asian in 5 of 18840 chromosomes (freq: 0.0003), Other in 1 of 6454 chromosomes (freq: 0.0002), European in 15 of 126098 chromosomes (freq: 0.0001), and African in 1 of 23930 chromosomes (freq: 0.00004), while the variant was not observed in the Ashkenazi Jewish, Finnish, Latino, or South Asian populations. The p.Arg245 residue is conserved across mammals and other organisms and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. Multiple studies have demonstrated that the p.Arg245His variant has functionally reduced or abolished DNA binding and glycosylase activity (Ali 2008, Komine 2015, Ruggieri 2013, Grasso 2014). In summary, based on the above information, this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic. -

Gastric cancer;C3272841:Familial adenomatous polyposis 2

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 29, 2024

- -

Neoplasm of stomach;C0206711:Pilomatrixoma;C3272841:Familial adenomatous polyposis 2

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 18, 2017

- -

MUTYH-related disorder

Pathogenic:1

Pathogenic, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 22, 2023

The MUTYH c.734G>A variant is predicted to result in the amino acid substitution p.Arg245His. This variant has been reported in the homozygous and compound heterozygous state in multiple patients to be causative for autosomal recessive adenomatous polyposis coli (sometimes reported as c.692G>A; p.Arg231His in Aceto et al. 2005. PubMed ID: 16134147; Kacerovska et al. 2016. PubMed ID: 27870730; Vogt et al. 2009. PubMed ID: 19732775). Functional studies of the p.Arg245His variant demonstrate that it is deficient in enzymatic and DNA binding activities (Ali et al. 2008. PubMed ID: 18534194), and that it is associated with a statistically significant increase in spontaneous mutation frequency in both homozygous and monoallelic heterozygous lymphoblastoid cell lines derived from MUTYH-associated polyposis patients (Grasso et al. 2014. PubMed ID: 24569162). This variant is reported in 0.025% of alleles in individuals of East Asian descent in gnomAD and has been interpreted as likely pathogenic and pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/140877/). This variant is interpreted as pathogenic. -

Diffuse midline glioma, H3 K27-altered

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Laboratory of Medical Genetics Unit, Bambino Gesù Children's Hospital

Feb 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

.;.;.;.;.;D;.;.;.;T;.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.99

.;D;.;D;D;D;D;D;D;D;D;D

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.89

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.8

.;.;.;.;.;H;.;.;.;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-4.7

D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Pathogenic

0.93

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0

.;.;.;.;.;D;D;.;D;.;.;.

Vest4

0.98

MVP

0.99

MPC

0.60

ClinPred

0.98

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.97

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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