TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8147	24664;24665;24666	chr2:178718761;178718760;178718759	chr2:179583488;179583487;179583486
N2AB	7830	23713;23714;23715	chr2:178718761;178718760;178718759	chr2:179583488;179583487;179583486
N2A	6903	20932;20933;20934	chr2:178718761;178718760;178718759	chr2:179583488;179583487;179583486
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-66
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4532
• 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/A	None	None	0.09	N	0.485	0.245	0.361360026772	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
D/E	None	None	0.001	N	0.174	0.119	0.141422826196	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
D/Y	None	None	0.912	N	0.621	0.363	0.653592515387	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	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
D/A	0.1812	likely_benign	0.2115	benign	-0.638	Destabilizing	0.09	N	0.485	neutral	N	0.514009637	None	None	N
D/C	0.6695	likely_pathogenic	0.7036	pathogenic	-0.131	Destabilizing	0.981	D	0.617	neutral	None	None	None	None	N
D/E	0.142	likely_benign	0.1582	benign	-0.672	Destabilizing	0.001	N	0.174	neutral	N	0.407380817	None	None	N
D/F	0.4682	ambiguous	0.5082	ambiguous	-0.45	Destabilizing	0.818	D	0.627	neutral	None	None	None	None	N
D/G	0.2246	likely_benign	0.2713	benign	-0.942	Destabilizing	0.324	N	0.526	neutral	D	0.533808906	None	None	N
D/H	0.2677	likely_benign	0.3145	benign	-0.758	Destabilizing	0.773	D	0.58	neutral	D	0.526266858	None	None	N
D/I	0.2412	likely_benign	0.2743	benign	0.153	Stabilizing	0.241	N	0.589	neutral	None	None	None	None	N
D/K	0.3379	likely_benign	0.4109	ambiguous	-0.251	Destabilizing	0.241	N	0.525	neutral	None	None	None	None	N
D/L	0.3243	likely_benign	0.3704	ambiguous	0.153	Stabilizing	0.241	N	0.553	neutral	None	None	None	None	N
D/M	0.5306	ambiguous	0.5752	pathogenic	0.65	Stabilizing	0.944	D	0.603	neutral	None	None	None	None	N
D/N	0.098	likely_benign	0.109	benign	-0.617	Destabilizing	0.324	N	0.508	neutral	N	0.483380085	None	None	N
D/P	0.6518	likely_pathogenic	0.7224	pathogenic	-0.087	Destabilizing	0.818	D	0.595	neutral	None	None	None	None	N
D/Q	0.3038	likely_benign	0.3597	ambiguous	-0.523	Destabilizing	0.241	N	0.507	neutral	None	None	None	None	N
D/R	0.364	ambiguous	0.444	ambiguous	-0.155	Destabilizing	0.69	D	0.621	neutral	None	None	None	None	N
D/S	0.1315	likely_benign	0.1496	benign	-0.822	Destabilizing	0.241	N	0.471	neutral	None	None	None	None	N
D/T	0.2156	likely_benign	0.2491	benign	-0.575	Destabilizing	0.008	N	0.313	neutral	None	None	None	None	N
D/V	0.1584	likely_benign	0.18	benign	-0.087	Destabilizing	0.006	N	0.385	neutral	N	0.467757272	None	None	N
D/W	0.8426	likely_pathogenic	0.8711	pathogenic	-0.281	Destabilizing	0.981	D	0.632	neutral	None	None	None	None	N
D/Y	0.1894	likely_benign	0.2031	benign	-0.214	Destabilizing	0.912	D	0.621	neutral	N	0.484491469	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.