TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7881	23866;23867;23868	chr2:178720001;178720000;178719999	chr2:179584728;179584727;179584726
N2AB	7564	22915;22916;22917	chr2:178720001;178720000;178719999	chr2:179584728;179584727;179584726
N2A	6637	20134;20135;20136	chr2:178720001;178720000;178719999	chr2:179584728;179584727;179584726
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-63
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.156
• 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
A/V	None	None	0.995	N	0.607	0.381	0.53279565985	gnomAD-4.0.0	1.59977E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87383E-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
A/C	0.7448	likely_pathogenic	0.6929	pathogenic	-1.352	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/D	0.9433	likely_pathogenic	0.935	pathogenic	-1.279	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
A/E	0.9475	likely_pathogenic	0.9303	pathogenic	-1.262	Destabilizing	1.0	D	0.751	deleterious	D	0.559549197	None	None	N
A/F	0.8919	likely_pathogenic	0.8749	pathogenic	-1.106	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/G	0.2123	likely_benign	0.2114	benign	-1.387	Destabilizing	0.009	N	0.305	neutral	N	0.510996877	None	None	N
A/H	0.9681	likely_pathogenic	0.9593	pathogenic	-1.456	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/I	0.7785	likely_pathogenic	0.702	pathogenic	-0.378	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/K	0.9817	likely_pathogenic	0.9743	pathogenic	-1.198	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
A/L	0.6812	likely_pathogenic	0.6275	pathogenic	-0.378	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/M	0.6575	likely_pathogenic	0.5924	pathogenic	-0.477	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
A/N	0.9	likely_pathogenic	0.8678	pathogenic	-1.071	Destabilizing	0.94	D	0.828	deleterious	None	None	None	None	N
A/P	0.9873	likely_pathogenic	0.9828	pathogenic	-0.57	Destabilizing	0.995	D	0.809	deleterious	D	0.559802687	None	None	N
A/Q	0.939	likely_pathogenic	0.9224	pathogenic	-1.176	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
A/R	0.9568	likely_pathogenic	0.9465	pathogenic	-0.948	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/S	0.1701	likely_benign	0.1603	benign	-1.547	Destabilizing	0.161	N	0.353	neutral	N	0.489814749	None	None	N
A/T	0.2114	likely_benign	0.1611	benign	-1.417	Destabilizing	0.904	D	0.559	neutral	N	0.515730137	None	None	N
A/V	0.4248	ambiguous	0.3466	ambiguous	-0.57	Destabilizing	0.995	D	0.607	neutral	N	0.492013114	None	None	N
A/W	0.9907	likely_pathogenic	0.9887	pathogenic	-1.441	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
A/Y	0.9597	likely_pathogenic	0.9511	pathogenic	-1.019	Destabilizing	1.0	D	0.855	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.