TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18303	55132;55133;55134	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
N2AB	16662	50209;50210;50211	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
N2A	15735	47428;47429;47430	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
N2B	9238	27937;27938;27939	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
Novex-1	9363	28312;28313;28314	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
Novex-2	9430	28513;28514;28515	chr2:178602495;178602494;178602493	chr2:179467222;179467221;179467220
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-21
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6638
• Predicted PPI site: I

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
P/L	None	None	0.085	N	0.517	0.439	0.560834375986	gnomAD-4.0.0	3.19368E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.73418E-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
P/A	0.069	likely_benign	0.0701	benign	-0.593	Destabilizing	0.928	D	0.574	neutral	N	0.471194655	None	None	I
P/C	0.4175	ambiguous	0.4146	ambiguous	-0.54	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
P/D	0.3408	ambiguous	0.3111	benign	-0.376	Destabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	I
P/E	0.2187	likely_benign	0.197	benign	-0.498	Destabilizing	0.992	D	0.7	prob.neutral	None	None	None	None	I
P/F	0.4248	ambiguous	0.4483	ambiguous	-0.85	Destabilizing	0.991	D	0.658	neutral	None	None	None	None	I
P/G	0.2767	likely_benign	0.287	benign	-0.735	Destabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	I
P/H	0.1679	likely_benign	0.1695	benign	-0.321	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
P/I	0.2311	likely_benign	0.2278	benign	-0.37	Destabilizing	0.968	D	0.672	neutral	None	None	None	None	I
P/K	0.1876	likely_benign	0.1731	benign	-0.431	Destabilizing	0.992	D	0.711	prob.delet.	None	None	None	None	I
P/L	0.1094	likely_benign	0.1126	benign	-0.37	Destabilizing	0.085	N	0.517	neutral	N	0.514368605	None	None	I
P/M	0.2652	likely_benign	0.2565	benign	-0.261	Destabilizing	0.996	D	0.651	neutral	None	None	None	None	I
P/N	0.279	likely_benign	0.2559	benign	-0.101	Destabilizing	0.997	D	0.7	prob.neutral	None	None	None	None	I
P/Q	0.1254	likely_benign	0.1243	benign	-0.392	Destabilizing	0.996	D	0.685	prob.neutral	N	0.493755908	None	None	I
P/R	0.131	likely_benign	0.1253	benign	0.125	Stabilizing	0.989	D	0.701	prob.neutral	N	0.491718446	None	None	I
P/S	0.1161	likely_benign	0.1182	benign	-0.479	Destabilizing	0.989	D	0.697	prob.neutral	N	0.488805157	None	None	I
P/T	0.0968	likely_benign	0.0963	benign	-0.502	Destabilizing	0.978	D	0.655	neutral	N	0.491527409	None	None	I
P/V	0.1558	likely_benign	0.15	benign	-0.409	Destabilizing	0.968	D	0.627	neutral	None	None	None	None	I
P/W	0.6155	likely_pathogenic	0.5994	pathogenic	-0.907	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
P/Y	0.4038	ambiguous	0.3985	ambiguous	-0.606	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	I

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.