TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26265	79018;79019;79020	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
N2AB	24624	74095;74096;74097	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
N2A	23697	71314;71315;71316	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
N2B	17200	51823;51824;51825	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
Novex-1	17325	52198;52199;52200	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
Novex-2	17392	52399;52400;52401	chr2:178567339;178567338;178567337	chr2:179432066;179432065;179432064
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-137
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.1761
• 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/F	None	None	0.884	N	0.481	0.227	0.390220360785	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.3782	ambiguous	0.3324	benign	-2.349	Highly Destabilizing	0.373	N	0.505	neutral	None	None	None	None	N
I/C	0.5955	likely_pathogenic	0.5307	ambiguous	-1.64	Destabilizing	0.996	D	0.544	neutral	None	None	None	None	N
I/D	0.7381	likely_pathogenic	0.6788	pathogenic	-2.487	Highly Destabilizing	0.953	D	0.621	neutral	None	None	None	None	N
I/E	0.5519	ambiguous	0.5084	ambiguous	-2.275	Highly Destabilizing	0.953	D	0.608	neutral	None	None	None	None	N
I/F	0.1888	likely_benign	0.157	benign	-1.341	Destabilizing	0.884	D	0.481	neutral	N	0.456906655	None	None	N
I/G	0.7052	likely_pathogenic	0.6386	pathogenic	-2.862	Highly Destabilizing	0.854	D	0.579	neutral	None	None	None	None	N
I/H	0.4229	ambiguous	0.3769	ambiguous	-2.323	Highly Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
I/K	0.4382	ambiguous	0.4049	ambiguous	-1.755	Destabilizing	0.91	D	0.617	neutral	None	None	None	None	N
I/L	0.1362	likely_benign	0.1225	benign	-0.877	Destabilizing	0.164	N	0.431	neutral	N	0.486760667	None	None	N
I/M	0.1144	likely_benign	0.1052	benign	-0.924	Destabilizing	0.939	D	0.498	neutral	N	0.484221794	None	None	N
I/N	0.2469	likely_benign	0.2198	benign	-2.047	Highly Destabilizing	0.939	D	0.624	neutral	N	0.506386578	None	None	N
I/P	0.9762	likely_pathogenic	0.9703	pathogenic	-1.347	Destabilizing	0.984	D	0.631	neutral	None	None	None	None	N
I/Q	0.4194	ambiguous	0.3801	ambiguous	-1.915	Destabilizing	0.984	D	0.659	neutral	None	None	None	None	N
I/R	0.355	ambiguous	0.3204	benign	-1.501	Destabilizing	0.953	D	0.638	neutral	None	None	None	None	N
I/S	0.2585	likely_benign	0.2214	benign	-2.727	Highly Destabilizing	0.521	D	0.533	neutral	N	0.460747502	None	None	N
I/T	0.1419	likely_benign	0.1407	benign	-2.379	Highly Destabilizing	0.012	N	0.312	neutral	N	0.361735301	None	None	N
I/V	0.0729	likely_benign	0.0703	benign	-1.347	Destabilizing	0.003	N	0.196	neutral	N	0.415476572	None	None	N
I/W	0.809	likely_pathogenic	0.7685	pathogenic	-1.709	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
I/Y	0.479	ambiguous	0.4245	ambiguous	-1.413	Destabilizing	0.953	D	0.537	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.