TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21509	64750;64751;64752	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
N2AB	19868	59827;59828;59829	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
N2A	18941	57046;57047;57048	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
N2B	12444	37555;37556;37557	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
Novex-1	12569	37930;37931;37932	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
Novex-2	12636	38131;38132;38133	chr2:178585219;178585218;178585217	chr2:179449946;179449945;179449944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-124
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.4594
• 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
T/I	None	None	0.059	N	0.213	0.19	0.337868961071	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
T/A	0.07	likely_benign	0.0725	benign	-0.215	Destabilizing	0.78	D	0.415	neutral	N	0.479974421	None	None	N
T/C	0.4125	ambiguous	0.4167	ambiguous	-0.299	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
T/D	0.3882	ambiguous	0.3809	ambiguous	0.359	Stabilizing	0.988	D	0.483	neutral	None	None	None	None	N
T/E	0.3038	likely_benign	0.2862	benign	0.28	Stabilizing	0.976	D	0.469	neutral	None	None	None	None	N
T/F	0.2352	likely_benign	0.2333	benign	-0.808	Destabilizing	0.976	D	0.591	neutral	None	None	None	None	N
T/G	0.2139	likely_benign	0.2135	benign	-0.312	Destabilizing	0.959	D	0.508	neutral	None	None	None	None	N
T/H	0.2798	likely_benign	0.2709	benign	-0.61	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
T/I	0.1692	likely_benign	0.1534	benign	-0.085	Destabilizing	0.059	N	0.213	neutral	N	0.501293842	None	None	N
T/K	0.2872	likely_benign	0.2737	benign	-0.226	Destabilizing	0.968	D	0.471	neutral	N	0.495597234	None	None	N
T/L	0.0891	likely_benign	0.0851	benign	-0.085	Destabilizing	0.702	D	0.426	neutral	None	None	None	None	N
T/M	0.0889	likely_benign	0.0929	benign	-0.062	Destabilizing	0.976	D	0.529	neutral	None	None	None	None	N
T/N	0.1134	likely_benign	0.115	benign	-0.07	Destabilizing	0.996	D	0.466	neutral	None	None	None	None	N
T/P	0.0641	likely_benign	0.0635	benign	-0.101	Destabilizing	0.059	N	0.215	neutral	N	0.444592411	None	None	N
T/Q	0.2275	likely_benign	0.2282	benign	-0.241	Destabilizing	0.996	D	0.522	neutral	None	None	None	None	N
T/R	0.2551	likely_benign	0.2429	benign	-0.041	Destabilizing	0.984	D	0.528	neutral	N	0.511548121	None	None	N
T/S	0.1011	likely_benign	0.1045	benign	-0.261	Destabilizing	0.896	D	0.402	neutral	N	0.435796782	None	None	N
T/V	0.1324	likely_benign	0.1226	benign	-0.101	Destabilizing	0.132	N	0.237	neutral	None	None	None	None	N
T/W	0.617	likely_pathogenic	0.6127	pathogenic	-0.867	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
T/Y	0.2773	likely_benign	0.277	benign	-0.546	Destabilizing	0.996	D	0.598	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.