TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7097	21514;21515;21516	chr2:178723970;178723969;178723968	chr2:179588697;179588696;179588695
N2AB	6780	20563;20564;20565	chr2:178723970;178723969;178723968	chr2:179588697;179588696;179588695
N2A	5853	17782;17783;17784	chr2:178723970;178723969;178723968	chr2:179588697;179588696;179588695
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-55
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3003
• 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
N/K	rs773211607	0.003	0.822	N	0.581	0.29	0.139678290688	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
N/K	rs773211607	0.003	0.822	N	0.581	0.29	0.139678290688	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
N/K	rs773211607	0.003	0.822	N	0.581	0.29	0.139678290688	gnomAD-4.0.0	2.47909E-06	None	None	None	None	N	None	0	1.66744E-05	None	0	2.22896E-05	None	0	0	0	0	3.20287E-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
N/A	0.3983	ambiguous	0.4285	ambiguous	-0.855	Destabilizing	0.076	N	0.48	neutral	None	None	None	None	N
N/C	0.5208	ambiguous	0.5502	ambiguous	0.025	Stabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
N/D	0.176	likely_benign	0.1832	benign	-0.215	Destabilizing	0.822	D	0.561	neutral	N	0.485603878	None	None	N
N/E	0.5985	likely_pathogenic	0.6314	pathogenic	-0.115	Destabilizing	0.86	D	0.581	neutral	None	None	None	None	N
N/F	0.7512	likely_pathogenic	0.7729	pathogenic	-0.682	Destabilizing	0.978	D	0.785	deleterious	None	None	None	None	N
N/G	0.3247	likely_benign	0.3176	benign	-1.191	Destabilizing	0.86	D	0.526	neutral	None	None	None	None	N
N/H	0.1598	likely_benign	0.1533	benign	-0.88	Destabilizing	0.99	D	0.621	neutral	D	0.52780355	None	None	N
N/I	0.5336	ambiguous	0.6188	pathogenic	-0.003	Destabilizing	0.942	D	0.777	deleterious	D	0.536615414	None	None	N
N/K	0.4887	ambiguous	0.5072	ambiguous	-0.113	Destabilizing	0.822	D	0.581	neutral	N	0.507328984	None	None	N
N/L	0.4494	ambiguous	0.5082	ambiguous	-0.003	Destabilizing	0.754	D	0.705	prob.neutral	None	None	None	None	N
N/M	0.5227	ambiguous	0.5659	pathogenic	0.341	Stabilizing	0.994	D	0.749	deleterious	None	None	None	None	N
N/P	0.8444	likely_pathogenic	0.8929	pathogenic	-0.257	Destabilizing	0.978	D	0.758	deleterious	None	None	None	None	N
N/Q	0.5088	ambiguous	0.5217	ambiguous	-0.673	Destabilizing	0.978	D	0.636	neutral	None	None	None	None	N
N/R	0.4698	ambiguous	0.4857	ambiguous	-0.17	Destabilizing	0.956	D	0.591	neutral	None	None	None	None	N
N/S	0.1018	likely_benign	0.1067	benign	-0.789	Destabilizing	0.489	N	0.561	neutral	N	0.493592822	None	None	N
N/T	0.2236	likely_benign	0.2648	benign	-0.484	Destabilizing	0.014	N	0.32	neutral	N	0.500051283	None	None	N
N/V	0.5279	ambiguous	0.6121	pathogenic	-0.257	Destabilizing	0.754	D	0.717	prob.delet.	None	None	None	None	N
N/W	0.8901	likely_pathogenic	0.8998	pathogenic	-0.453	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
N/Y	0.3008	likely_benign	0.3172	benign	-0.234	Destabilizing	0.99	D	0.759	deleterious	N	0.516447244	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.