TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2457	7594;7595;7596	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
N2AB	2457	7594;7595;7596	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
N2A	2457	7594;7595;7596	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
N2B	2411	7456;7457;7458	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
Novex-1	2411	7456;7457;7458	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
Novex-2	2411	7456;7457;7458	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412
Novex-3	2457	7594;7595;7596	chr2:178773687;178773686;178773685	chr2:179638414;179638413;179638412

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-14
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5519
• 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/T	None	None	0.117	N	0.417	0.16	0.688619951122	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2801	likely_benign	0.2719	benign	-0.855	Destabilizing	0.035	N	0.422	neutral	None	None	None	None	N
I/C	0.7406	likely_pathogenic	0.7323	pathogenic	-0.679	Destabilizing	0.824	D	0.411	neutral	None	None	None	None	N
I/D	0.8137	likely_pathogenic	0.7999	pathogenic	-0.299	Destabilizing	0.791	D	0.489	neutral	None	None	None	None	N
I/E	0.6272	likely_pathogenic	0.6058	pathogenic	-0.385	Destabilizing	0.555	D	0.485	neutral	None	None	None	None	N
I/F	0.1926	likely_benign	0.1803	benign	-0.778	Destabilizing	0.188	N	0.373	neutral	N	0.51121623	None	None	N
I/G	0.7331	likely_pathogenic	0.7167	pathogenic	-1.043	Destabilizing	0.555	D	0.477	neutral	None	None	None	None	N
I/H	0.6053	likely_pathogenic	0.5895	pathogenic	-0.277	Destabilizing	0.935	D	0.481	neutral	None	None	None	None	N
I/K	0.3466	ambiguous	0.3299	benign	-0.506	Destabilizing	0.555	D	0.475	neutral	None	None	None	None	N
I/L	0.0925	likely_benign	0.0875	benign	-0.478	Destabilizing	None	N	0.188	neutral	N	0.492445608	None	None	N
I/M	0.1006	likely_benign	0.0967	benign	-0.422	Destabilizing	0.188	N	0.413	neutral	N	0.506009482	None	None	N
I/N	0.4321	ambiguous	0.4169	ambiguous	-0.3	Destabilizing	0.741	D	0.483	neutral	N	0.504170429	None	None	N
I/P	0.6581	likely_pathogenic	0.6405	pathogenic	-0.57	Destabilizing	0.791	D	0.485	neutral	None	None	None	None	N
I/Q	0.4619	ambiguous	0.4426	ambiguous	-0.544	Destabilizing	0.791	D	0.481	neutral	None	None	None	None	N
I/R	0.2653	likely_benign	0.2495	benign	0.1	Stabilizing	0.555	D	0.482	neutral	None	None	None	None	N
I/S	0.366	ambiguous	0.3542	ambiguous	-0.788	Destabilizing	0.317	N	0.478	neutral	N	0.498520943	None	None	N
I/T	0.1212	likely_benign	0.1197	benign	-0.766	Destabilizing	0.117	N	0.417	neutral	N	0.469401489	None	None	N
I/V	0.0782	likely_benign	0.0779	benign	-0.57	Destabilizing	None	N	0.205	neutral	N	0.447169318	None	None	N
I/W	0.7385	likely_pathogenic	0.7276	pathogenic	-0.776	Destabilizing	0.935	D	0.529	neutral	None	None	None	None	N
I/Y	0.571	likely_pathogenic	0.5525	ambiguous	-0.541	Destabilizing	0.555	D	0.432	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.