TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9593	29002;29003;29004	chr2:178707790;178707789;178707788	chr2:179572517;179572516;179572515
N2AB	9276	28051;28052;28053	chr2:178707790;178707789;178707788	chr2:179572517;179572516;179572515
N2A	8349	25270;25271;25272	chr2:178707790;178707789;178707788	chr2:179572517;179572516;179572515
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-82
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5132
• 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	None	None	1.0	None	0.383	0.174	0.159798565429	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/N	None	None	1.0	None	0.635	0.287	0.177238962908	gnomAD-4.0.0	1.38024E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8132E-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
D/A	0.4392	ambiguous	0.335	benign	-0.62	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/C	0.8799	likely_pathogenic	0.8247	pathogenic	-0.476	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/E	0.366	ambiguous	0.3092	benign	-0.771	Destabilizing	1.0	D	0.383	neutral	None	None	None	None	N
D/F	0.8003	likely_pathogenic	0.7081	pathogenic	-0.399	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
D/G	0.4135	ambiguous	0.3154	benign	-0.937	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/H	0.4705	ambiguous	0.3779	ambiguous	-0.849	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
D/I	0.5941	likely_pathogenic	0.4753	ambiguous	0.211	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
D/K	0.6713	likely_pathogenic	0.5907	pathogenic	-1.114	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/L	0.5755	likely_pathogenic	0.4806	ambiguous	0.211	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/M	0.8563	likely_pathogenic	0.79	pathogenic	0.63	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
D/N	0.1593	likely_benign	0.1274	benign	-1.227	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
D/P	0.925	likely_pathogenic	0.9162	pathogenic	-0.043	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
D/Q	0.5862	likely_pathogenic	0.5013	ambiguous	-1.079	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
D/R	0.6442	likely_pathogenic	0.5565	ambiguous	-0.902	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/S	0.2052	likely_benign	0.1623	benign	-1.494	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
D/T	0.4307	ambiguous	0.3484	ambiguous	-1.262	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
D/V	0.4179	ambiguous	0.3097	benign	-0.043	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/W	0.9594	likely_pathogenic	0.9417	pathogenic	-0.362	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/Y	0.4325	ambiguous	0.3436	ambiguous	-0.277	Destabilizing	1.0	D	0.747	deleterious	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.