TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21510	64753;64754;64755	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
N2AB	19869	59830;59831;59832	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
N2A	18942	57049;57050;57051	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
N2B	12445	37558;37559;37560	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
Novex-1	12570	37933;37934;37935	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
Novex-2	12637	38134;38135;38136	chr2:178585216;178585215;178585214	chr2:179449943;179449942;179449941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-124
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.3477
• 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
S/P	None	None	1.0	N	0.727	0.518	0.36893422563	gnomAD-4.0.0	1.59229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43353E-05	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
S/A	0.1479	likely_benign	0.145	benign	-0.244	Destabilizing	0.997	D	0.409	neutral	N	0.516875717	None	None	N
S/C	0.2405	likely_benign	0.2094	benign	-0.267	Destabilizing	1.0	D	0.705	prob.neutral	N	0.505137169	None	None	N
S/D	0.5526	ambiguous	0.4848	ambiguous	0.142	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
S/E	0.8327	likely_pathogenic	0.7989	pathogenic	0.036	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
S/F	0.6218	likely_pathogenic	0.6031	pathogenic	-0.954	Destabilizing	1.0	D	0.74	deleterious	N	0.482006485	None	None	N
S/G	0.1307	likely_benign	0.1213	benign	-0.314	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
S/H	0.6467	likely_pathogenic	0.5847	pathogenic	-0.785	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
S/I	0.6061	likely_pathogenic	0.5891	pathogenic	-0.196	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
S/K	0.9091	likely_pathogenic	0.8791	pathogenic	-0.38	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
S/L	0.268	likely_benign	0.2623	benign	-0.196	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
S/M	0.4762	ambiguous	0.4652	ambiguous	-0.031	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
S/N	0.275	likely_benign	0.2486	benign	-0.119	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
S/P	0.8652	likely_pathogenic	0.851	pathogenic	-0.186	Destabilizing	1.0	D	0.727	prob.delet.	N	0.474662651	None	None	N
S/Q	0.7859	likely_pathogenic	0.7562	pathogenic	-0.355	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
S/R	0.8856	likely_pathogenic	0.8558	pathogenic	-0.183	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/T	0.1051	likely_benign	0.1042	benign	-0.221	Destabilizing	0.999	D	0.431	neutral	N	0.497500523	None	None	N
S/V	0.4857	ambiguous	0.4737	ambiguous	-0.186	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
S/W	0.772	likely_pathogenic	0.7401	pathogenic	-1.008	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
S/Y	0.5328	ambiguous	0.4969	ambiguous	-0.7	Destabilizing	1.0	D	0.738	prob.delet.	N	0.478385634	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.