TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17983	54172;54173;54174	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
N2AB	16342	49249;49250;49251	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
N2A	15415	46468;46469;46470	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
N2B	8918	26977;26978;26979	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
Novex-1	9043	27352;27353;27354	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
Novex-2	9110	27553;27554;27555	chr2:178605230;178605229;178605228	chr2:179469957;179469956;179469955
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-114
• Domain position: 16
• Structural Position: 26
• Q(SASA): 0.4456
• 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
P/A	None	None	0.4	N	0.319	0.14	0.177238962908	gnomAD-4.0.0	6.85439E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00403E-07	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	0.0608	likely_benign	0.0589	benign	-1.274	Destabilizing	0.4	N	0.319	neutral	N	0.418306234	None	None	N
P/C	0.5154	ambiguous	0.475	ambiguous	-0.67	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
P/D	0.369	ambiguous	0.3125	benign	-1.401	Destabilizing	0.996	D	0.53	neutral	None	None	None	None	N
P/E	0.2722	likely_benign	0.2321	benign	-1.447	Destabilizing	0.996	D	0.523	neutral	None	None	None	None	N
P/F	0.4749	ambiguous	0.4328	ambiguous	-1.106	Destabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
P/G	0.2831	likely_benign	0.2483	benign	-1.536	Destabilizing	0.985	D	0.54	neutral	None	None	None	None	N
P/H	0.2423	likely_benign	0.2054	benign	-1.165	Destabilizing	1.0	D	0.666	neutral	N	0.503039629	None	None	N
P/I	0.2632	likely_benign	0.2599	benign	-0.669	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	N
P/K	0.2842	likely_benign	0.2373	benign	-1.226	Destabilizing	0.996	D	0.502	neutral	None	None	None	None	N
P/L	0.1312	likely_benign	0.1182	benign	-0.669	Destabilizing	0.135	N	0.415	neutral	N	0.486262022	None	None	N
P/M	0.2573	likely_benign	0.2366	benign	-0.389	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
P/N	0.2789	likely_benign	0.2357	benign	-0.879	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
P/Q	0.1873	likely_benign	0.1574	benign	-1.11	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	N
P/R	0.2173	likely_benign	0.1829	benign	-0.611	Destabilizing	0.997	D	0.673	neutral	N	0.456651191	None	None	N
P/S	0.1226	likely_benign	0.1083	benign	-1.253	Destabilizing	0.817	D	0.295	neutral	N	0.426480213	None	None	N
P/T	0.0992	likely_benign	0.0891	benign	-1.207	Destabilizing	0.961	D	0.493	neutral	N	0.426653571	None	None	N
P/V	0.1734	likely_benign	0.1699	benign	-0.837	Destabilizing	0.971	D	0.545	neutral	None	None	None	None	N
P/W	0.7225	likely_pathogenic	0.6499	pathogenic	-1.292	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
P/Y	0.4674	ambiguous	0.4158	ambiguous	-1.034	Destabilizing	0.999	D	0.702	prob.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.