TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14189	42790;42791;42792	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
N2AB	12548	37867;37868;37869	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
N2A	11621	35086;35087;35088	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
N2B	5124	15595;15596;15597	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
Novex-1	5249	15970;15971;15972	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
Novex-2	5316	16171;16172;16173	chr2:178633934;178633933;178633932	chr2:179498661;179498660;179498659
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-92
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.2616
• Predicted PPI site: N

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
I/F	None	None	None	N	0.123	0.163	0.529861178392	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-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
I/A	0.508	ambiguous	0.4511	ambiguous	-1.793	Destabilizing	0.016	N	0.339	neutral	None	None	None	None	N
I/C	0.7223	likely_pathogenic	0.5847	pathogenic	-1.158	Destabilizing	0.356	N	0.526	neutral	None	None	None	None	N
I/D	0.8766	likely_pathogenic	0.8421	pathogenic	-0.987	Destabilizing	0.214	N	0.623	neutral	None	None	None	None	N
I/E	0.7111	likely_pathogenic	0.6913	pathogenic	-0.851	Destabilizing	0.072	N	0.586	neutral	None	None	None	None	N
I/F	0.1451	likely_benign	0.0623	benign	-0.999	Destabilizing	None	N	0.123	neutral	N	0.51573515	None	None	N
I/G	0.8172	likely_pathogenic	0.7573	pathogenic	-2.248	Highly Destabilizing	0.072	N	0.541	neutral	None	None	None	None	N
I/H	0.5753	likely_pathogenic	0.4457	ambiguous	-1.459	Destabilizing	0.628	D	0.593	neutral	None	None	None	None	N
I/K	0.4857	ambiguous	0.459	ambiguous	-1.097	Destabilizing	0.072	N	0.581	neutral	None	None	None	None	N
I/L	0.097	likely_benign	0.0917	benign	-0.552	Destabilizing	0.001	N	0.275	neutral	N	0.512367928	None	None	N
I/M	0.0719	likely_benign	0.0634	benign	-0.557	Destabilizing	0.001	N	0.202	neutral	N	0.499478153	None	None	N
I/N	0.4856	ambiguous	0.4051	ambiguous	-1.165	Destabilizing	0.171	N	0.627	neutral	D	0.660716817	None	None	N
I/P	0.8664	likely_pathogenic	0.8589	pathogenic	-0.938	Destabilizing	0.356	N	0.623	neutral	None	None	None	None	N
I/Q	0.4485	ambiguous	0.4168	ambiguous	-1.114	Destabilizing	0.214	N	0.618	neutral	None	None	None	None	N
I/R	0.4157	ambiguous	0.3565	ambiguous	-0.802	Destabilizing	0.214	N	0.627	neutral	None	None	None	None	N
I/S	0.4505	ambiguous	0.382	ambiguous	-1.943	Destabilizing	0.029	N	0.481	neutral	D	0.579033147	None	None	N
I/T	0.3445	ambiguous	0.2947	benign	-1.657	Destabilizing	None	N	0.193	neutral	N	0.509599416	None	None	N
I/V	0.1072	likely_benign	0.1004	benign	-0.938	Destabilizing	0.005	N	0.283	neutral	N	0.503537264	None	None	N
I/W	0.715	likely_pathogenic	0.5449	ambiguous	-1.17	Destabilizing	0.864	D	0.598	neutral	None	None	None	None	N
I/Y	0.4705	ambiguous	0.3034	benign	-0.882	Destabilizing	0.038	N	0.53	neutral	None	None	None	None	N

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.