TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33014	99265;99266;99267	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
N2AB	31373	94342;94343;94344	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
N2A	30446	91561;91562;91563	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
N2B	23949	72070;72071;72072	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
Novex-1	24074	72445;72446;72447	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
Novex-2	24141	72646;72647;72648	chr2:178538789;178538788;178538787	chr2:179403516;179403515;179403514
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-129
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1678
• 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/T	None	None	0.994	N	0.461	0.281	0.3349148499	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.97034E-05

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	0.0867	likely_benign	0.0964	benign	-0.873	Destabilizing	0.98	D	0.392	neutral	None	None	None	None	N
S/C	0.0939	likely_benign	0.0999	benign	-0.867	Destabilizing	0.391	N	0.402	neutral	N	0.517065797	None	None	N
S/D	0.635	likely_pathogenic	0.7374	pathogenic	-0.853	Destabilizing	1.0	D	0.556	neutral	None	None	None	None	N
S/E	0.6463	likely_pathogenic	0.7343	pathogenic	-0.864	Destabilizing	1.0	D	0.564	neutral	None	None	None	None	N
S/F	0.1936	likely_benign	0.2409	benign	-1.366	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
S/G	0.1344	likely_benign	0.1572	benign	-1.051	Destabilizing	0.994	D	0.435	neutral	N	0.48167295	None	None	N
S/H	0.3952	ambiguous	0.4599	ambiguous	-1.576	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/I	0.2261	likely_benign	0.3031	benign	-0.503	Destabilizing	0.998	D	0.742	deleterious	N	0.493055708	None	None	N
S/K	0.767	likely_pathogenic	0.849	pathogenic	-0.655	Destabilizing	1.0	D	0.541	neutral	None	None	None	None	N
S/L	0.1326	likely_benign	0.1743	benign	-0.503	Destabilizing	0.992	D	0.647	neutral	None	None	None	None	N
S/M	0.1962	likely_benign	0.2259	benign	-0.133	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
S/N	0.19	likely_benign	0.2425	benign	-0.726	Destabilizing	0.999	D	0.555	neutral	N	0.480267371	None	None	N
S/P	0.9838	likely_pathogenic	0.9919	pathogenic	-0.598	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
S/Q	0.5592	ambiguous	0.6263	pathogenic	-1.027	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
S/R	0.6586	likely_pathogenic	0.7752	pathogenic	-0.474	Destabilizing	0.999	D	0.721	prob.delet.	N	0.479279866	None	None	N
S/T	0.0916	likely_benign	0.1009	benign	-0.735	Destabilizing	0.994	D	0.461	neutral	N	0.49697574	None	None	N
S/V	0.2209	likely_benign	0.2768	benign	-0.598	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
S/W	0.4557	ambiguous	0.5548	ambiguous	-1.313	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
S/Y	0.1826	likely_benign	0.234	benign	-1.01	Destabilizing	1.0	D	0.748	deleterious	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.