SVIL

supervillin, the group of Gelsolin/villins|MicroRNA protein coding host genes

Basic information

Region (hg38): 10:29457337-29736959

Links

ENSG00000197321 ∙ NCBI:6840 ∙ OMIM:604126 ∙ HGNC:11480 ∙ Uniprot:O95425 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myofibrillar myopathy 10 (Strong), mode of inheritance: AR
• myofibrillar myopathy 10 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myofibrillar myopathy 10	AR	Cardiovascular	The condition can involve cardiovascular sequelae, including ventricular hypertrophy with EKG abnormalities, and elevated cardiac enzymes, and awareness may allow early diagnosis and management	Cardiovascular; Musculoskeletal	32779703

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SVIL gene.

• not provided (150 variants)
• Inborn genetic diseases (102 variants)
• Myofibrillar myopathy 10 (6 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SVIL gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	9	27	37
missense		1	102	9	12	124
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		2				2
splice region					1	1
non coding				2	89	91
Total	0	3	103	20	128

Highest pathogenic variant AF is 0.000105

Variants in SVIL

This is a list of pathogenic ClinVar variants found in the SVIL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-29458226-GCTC-G			Benign (May 15, 2021)
10-29458290-G-A		not specified	Uncertain significance (Oct 05, 2022)
10-29458291-C-T		not specified	Uncertain significance (Dec 27, 2023)
10-29458292-G-A			Benign (May 04, 2021)
10-29458332-A-G		not specified	Uncertain significance (Jan 19, 2024)
10-29458383-GT-G			Benign (May 16, 2021)
10-29458386-C-T			Benign (May 16, 2021)
10-29458436-C-T		not specified	Uncertain significance (Dec 13, 2023)
10-29458448-C-T		not specified	Uncertain significance (Dec 19, 2022)
10-29458449-G-A			Likely benign (Jul 31, 2017)
10-29458486-T-G		not specified	Uncertain significance (Feb 28, 2023)
10-29458488-C-T			Benign (May 04, 2021)
10-29458508-G-A		not specified	Uncertain significance (Nov 09, 2021)
10-29458511-C-T		not specified	Uncertain significance (Nov 14, 2023)
10-29458518-C-T			Likely benign (Apr 02, 2018)
10-29458544-C-T		not specified	Uncertain significance (Feb 16, 2023)
10-29458551-G-A			Benign (Mar 29, 2018)
10-29458689-T-A			Benign (May 15, 2021)
10-29462163-G-C			Benign (May 15, 2021)
10-29462267-G-A			Likely benign (Apr 02, 2018)
10-29462326-A-G		not specified	Uncertain significance (Mar 20, 2023)
10-29462332-G-A		not specified	Uncertain significance (Oct 02, 2023)
10-29462361-G-A			Benign (Apr 20, 2018)
10-29462378-G-T		not specified	Uncertain significance (Jan 03, 2022)
10-29462393-G-C		not specified	Uncertain significance (Jun 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SVIL	protein_coding	protein_coding	ENST00000375398	35	279444

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000863	0.999	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.885	1202	1.29e+3	0.931	0.0000799	14427
Missense in Polyphen		344	411	0.83698		4624
Synonymous	-0.619	554	536	1.03	0.0000380	4362
Loss of Function	7.19	29	111	0.262	0.00000639	1252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000421	0.000420
Ashkenazi Jewish	0.000727	0.000695
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000354	0.000352
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Forms a high-affinity link between the actin cytoskeleton and the membrane. Is among the first costameric proteins to assemble during myogenesis and it contributes to myogenic membrane structure and differentiation (PubMed:12711699). Appears to be involved in myosin II assembly. May modulate myosin II regulation through MLCK during cell spreading, an initial step in cell migration. May play a role in invadopodial function (PubMed:19109420). {ECO:0000269|PubMed:12711699, ECO:0000269|PubMed:19109420}.
• Pathway: AndrogenReceptor;Coregulation of Androgen receptor activity (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.573
• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.34

Haploinsufficiency Scores

• pHI: 0.146
• hipred: Y
• hipred_score: 0.603
• ghis: 0.536

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.820

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: Svil
• Phenotype: hematopoietic system phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: svila
• Affected structure: pericardium
• Phenotype tag: abnormal
• Phenotype quality: edematous

Gene ontology

• Biological process: cytoskeleton organization;skeletal muscle tissue development;positive regulation of cytokinesis
• Cellular component: podosome;nucleus;cytoplasm;cytosol;plasma membrane;focal adhesion;actin cytoskeleton;midbody;cleavage furrow;microtubule minus-end;costamere;invadopodium
• Molecular function: protein binding;actin filament binding