TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35300	106123;106124;106125	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
N2AB	33659	101200;101201;101202	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
N2A	32732	98419;98420;98421	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
N2B	26235	78928;78929;78930	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
Novex-1	26360	79303;79304;79305	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
Novex-2	26427	79504;79505;79506	chr2:178530717;178530716;178530715	chr2:179395444;179395443;179395442
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-165
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3825
• 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
I/M	rs769262485	-0.339	0.045	N	0.286	0.08	0.0846915920261	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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
I/A	0.1792	likely_benign	0.1752	benign	-1.594	Destabilizing	0.002	N	0.239	neutral	None	None	None	None	N
I/C	0.6452	likely_pathogenic	0.6453	pathogenic	-0.878	Destabilizing	0.112	N	0.303	neutral	None	None	None	None	N
I/D	0.4511	ambiguous	0.4186	ambiguous	-1.08	Destabilizing	0.017	N	0.407	neutral	None	None	None	None	N
I/E	0.3224	likely_benign	0.306	benign	-1.121	Destabilizing	0.004	N	0.345	neutral	None	None	None	None	N
I/F	0.14	likely_benign	0.1376	benign	-1.307	Destabilizing	None	N	0.122	neutral	N	0.489748697	None	None	N
I/G	0.5092	ambiguous	0.4849	ambiguous	-1.874	Destabilizing	0.007	N	0.373	neutral	None	None	None	None	N
I/H	0.4011	ambiguous	0.3953	ambiguous	-1.12	Destabilizing	0.112	N	0.383	neutral	None	None	None	None	N
I/K	0.231	likely_benign	0.2185	benign	-0.983	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
I/L	0.1547	likely_benign	0.1507	benign	-0.916	Destabilizing	None	N	0.086	neutral	N	0.484380163	None	None	N
I/M	0.0819	likely_benign	0.0831	benign	-0.595	Destabilizing	0.045	N	0.286	neutral	N	0.480590496	None	None	N
I/N	0.1434	likely_benign	0.1326	benign	-0.696	Destabilizing	0.013	N	0.437	neutral	N	0.441474748	None	None	N
I/P	0.7839	likely_pathogenic	0.7123	pathogenic	-1.11	Destabilizing	0.035	N	0.454	neutral	None	None	None	None	N
I/Q	0.3246	likely_benign	0.3219	benign	-0.959	Destabilizing	0.017	N	0.469	neutral	None	None	None	None	N
I/R	0.1882	likely_benign	0.1778	benign	-0.347	Destabilizing	0.009	N	0.411	neutral	None	None	None	None	N
I/S	0.1742	likely_benign	0.166	benign	-1.274	Destabilizing	None	N	0.153	neutral	N	0.39186986	None	None	N
I/T	0.0811	likely_benign	0.0781	benign	-1.207	Destabilizing	None	N	0.126	neutral	N	0.382386372	None	None	N
I/V	0.0857	likely_benign	0.091	benign	-1.11	Destabilizing	None	N	0.091	neutral	N	0.461137944	None	None	N
I/W	0.6769	likely_pathogenic	0.6638	pathogenic	-1.323	Destabilizing	0.278	N	0.359	neutral	None	None	None	None	N
I/Y	0.386	ambiguous	0.3658	ambiguous	-1.109	Destabilizing	None	N	0.159	neutral	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.