TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8368	25327;25328;25329	chr2:178717772;178717771;178717770	chr2:179582499;179582498;179582497
N2AB	8051	24376;24377;24378	chr2:178717772;178717771;178717770	chr2:179582499;179582498;179582497
N2A	7124	21595;21596;21597	chr2:178717772;178717771;178717770	chr2:179582499;179582498;179582497
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-69
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5242
• 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
D/E	rs369089044	-0.066	0.992	N	0.365	0.241	0.0806252709748	gnomAD-2.1.1	3.29E-05	None	None	None	None	N	None	6.57E-05	0	None	0	0	None	0	None	0	6.38E-05	0
D/E	rs369089044	-0.066	0.992	N	0.365	0.241	0.0806252709748	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	7.35E-05	0	0
D/E	rs369089044	-0.066	0.992	N	0.365	0.241	0.0806252709748	gnomAD-4.0.0	3.79157E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.92553E-05	0	4.82129E-05

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
D/A	0.4152	ambiguous	0.5519	ambiguous	-0.459	Destabilizing	0.999	D	0.546	neutral	N	0.458047701	None	None	N
D/C	0.9403	likely_pathogenic	0.9667	pathogenic	-0.329	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
D/E	0.3264	likely_benign	0.3977	ambiguous	-0.515	Destabilizing	0.992	D	0.365	neutral	N	0.453893418	None	None	N
D/F	0.9324	likely_pathogenic	0.9674	pathogenic	-0.025	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/G	0.4152	ambiguous	0.5733	pathogenic	-0.766	Destabilizing	0.997	D	0.438	neutral	N	0.464377577	None	None	N
D/H	0.6972	likely_pathogenic	0.8075	pathogenic	-0.137	Destabilizing	1.0	D	0.647	neutral	N	0.467695713	None	None	N
D/I	0.8209	likely_pathogenic	0.8942	pathogenic	0.34	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/K	0.8575	likely_pathogenic	0.9294	pathogenic	-0.456	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
D/L	0.8364	likely_pathogenic	0.9117	pathogenic	0.34	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
D/M	0.9205	likely_pathogenic	0.9529	pathogenic	0.535	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/N	0.2073	likely_benign	0.2632	benign	-0.777	Destabilizing	0.725	D	0.263	neutral	N	0.470185344	None	None	N
D/P	0.7235	likely_pathogenic	0.8325	pathogenic	0.098	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
D/Q	0.7832	likely_pathogenic	0.8758	pathogenic	-0.65	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
D/R	0.8742	likely_pathogenic	0.9426	pathogenic	-0.141	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
D/S	0.3343	likely_benign	0.4319	ambiguous	-0.99	Destabilizing	0.998	D	0.373	neutral	None	None	None	None	N
D/T	0.5934	likely_pathogenic	0.7031	pathogenic	-0.749	Destabilizing	0.996	D	0.59	neutral	None	None	None	None	N
D/V	0.6009	likely_pathogenic	0.729	pathogenic	0.098	Stabilizing	1.0	D	0.705	prob.neutral	N	0.467442223	None	None	N
D/W	0.9823	likely_pathogenic	0.9921	pathogenic	0.146	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
D/Y	0.6176	likely_pathogenic	0.767	pathogenic	0.186	Stabilizing	1.0	D	0.691	prob.neutral	N	0.499878525	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.