TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6318	19177;19178;19179	chr2:178729086;178729085;178729084	chr2:179593813;179593812;179593811
N2AB	6001	18226;18227;18228	chr2:178729086;178729085;178729084	chr2:179593813;179593812;179593811
N2A	5074	15445;15446;15447	chr2:178729086;178729085;178729084	chr2:179593813;179593812;179593811
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-47
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.4661
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
S/C	None	None	0.996	N	0.54	0.429	0.706475442758	gnomAD-4.0.0	3.19025E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72646E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
S/A	0.1351	likely_benign	0.1124	benign	-0.167	Destabilizing	0.026	N	0.241	neutral	N	0.478166267	None	None	I
S/C	0.2675	likely_benign	0.2087	benign	-0.327	Destabilizing	0.996	D	0.54	neutral	N	0.510357631	None	None	I
S/D	0.6808	likely_pathogenic	0.7147	pathogenic	0.09	Stabilizing	0.959	D	0.486	neutral	None	None	None	None	I
S/E	0.7809	likely_pathogenic	0.794	pathogenic	0.001	Stabilizing	0.919	D	0.492	neutral	None	None	None	None	I
S/F	0.2561	likely_benign	0.2448	benign	-0.767	Destabilizing	0.984	D	0.676	prob.neutral	N	0.504334148	None	None	I
S/G	0.2439	likely_benign	0.2204	benign	-0.27	Destabilizing	0.851	D	0.472	neutral	None	None	None	None	I
S/H	0.5609	ambiguous	0.5714	pathogenic	-0.665	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	I
S/I	0.3574	ambiguous	0.3044	benign	-0.028	Destabilizing	0.976	D	0.657	neutral	None	None	None	None	I
S/K	0.8841	likely_pathogenic	0.8944	pathogenic	-0.48	Destabilizing	0.919	D	0.489	neutral	None	None	None	None	I
S/L	0.1442	likely_benign	0.1295	benign	-0.028	Destabilizing	0.851	D	0.633	neutral	None	None	None	None	I
S/M	0.3282	likely_benign	0.299	benign	-0.057	Destabilizing	0.999	D	0.528	neutral	None	None	None	None	I
S/N	0.348	ambiguous	0.3395	benign	-0.194	Destabilizing	0.959	D	0.52	neutral	None	None	None	None	I
S/P	0.7932	likely_pathogenic	0.7853	pathogenic	-0.045	Destabilizing	0.984	D	0.515	neutral	D	0.529557879	None	None	I
S/Q	0.7396	likely_pathogenic	0.7401	pathogenic	-0.397	Destabilizing	0.988	D	0.47	neutral	None	None	None	None	I
S/R	0.8481	likely_pathogenic	0.8559	pathogenic	-0.251	Destabilizing	0.988	D	0.517	neutral	None	None	None	None	I
S/T	0.0989	likely_benign	0.1066	benign	-0.267	Destabilizing	0.103	N	0.261	neutral	D	0.52216776	None	None	I
S/V	0.3448	ambiguous	0.2853	benign	-0.045	Destabilizing	0.851	D	0.628	neutral	None	None	None	None	I
S/W	0.4891	ambiguous	0.4942	ambiguous	-0.846	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
S/Y	0.2615	likely_benign	0.2498	benign	-0.536	Destabilizing	0.995	D	0.669	neutral	D	0.52722965	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.