TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25101	75526;75527;75528	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
N2AB	23460	70603;70604;70605	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
N2A	22533	67822;67823;67824	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
N2B	16036	48331;48332;48333	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
Novex-1	16161	48706;48707;48708	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
Novex-2	16228	48907;48908;48909	chr2:178570831;178570830;178570829	chr2:179435558;179435557;179435556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-70
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.2974
• 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
T/I	rs1286105524	0.09	0.071	N	0.315	0.278	0.300449992093	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs1286105524	0.09	0.071	N	0.315	0.278	0.300449992093	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8592E-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
T/A	0.1682	likely_benign	0.1508	benign	-0.788	Destabilizing	0.914	D	0.505	neutral	N	0.465226265	None	None	N
T/C	0.6564	likely_pathogenic	0.5739	pathogenic	-0.551	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/D	0.8053	likely_pathogenic	0.7392	pathogenic	-0.334	Destabilizing	0.997	D	0.738	deleterious	None	None	None	None	N
T/E	0.6455	likely_pathogenic	0.56	ambiguous	-0.323	Destabilizing	0.997	D	0.729	deleterious	None	None	None	None	N
T/F	0.4607	ambiguous	0.3933	ambiguous	-0.75	Destabilizing	0.98	D	0.783	deleterious	None	None	None	None	N
T/G	0.6572	likely_pathogenic	0.5945	pathogenic	-1.065	Destabilizing	0.99	D	0.552	neutral	None	None	None	None	N
T/H	0.5646	likely_pathogenic	0.4881	ambiguous	-1.328	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
T/I	0.2225	likely_benign	0.1957	benign	-0.14	Destabilizing	0.071	N	0.315	neutral	N	0.487502534	None	None	N
T/K	0.4732	ambiguous	0.3993	ambiguous	-0.832	Destabilizing	0.987	D	0.735	deleterious	D	0.522231183	None	None	N
T/L	0.1453	likely_benign	0.1312	benign	-0.14	Destabilizing	0.707	D	0.543	neutral	None	None	None	None	N
T/M	0.1199	likely_benign	0.1114	benign	0.082	Stabilizing	0.995	D	0.771	deleterious	None	None	None	None	N
T/N	0.3952	ambiguous	0.3444	ambiguous	-0.782	Destabilizing	0.997	D	0.741	deleterious	None	None	None	None	N
T/P	0.3444	ambiguous	0.2876	benign	-0.323	Destabilizing	0.996	D	0.771	deleterious	N	0.479963159	None	None	N
T/Q	0.4643	ambiguous	0.4036	ambiguous	-0.926	Destabilizing	0.997	D	0.78	deleterious	None	None	None	None	N
T/R	0.4084	ambiguous	0.3435	ambiguous	-0.608	Destabilizing	0.996	D	0.768	deleterious	N	0.474620787	None	None	N
T/S	0.2814	likely_benign	0.2424	benign	-1.049	Destabilizing	0.955	D	0.503	neutral	N	0.494940315	None	None	N
T/V	0.1687	likely_benign	0.1527	benign	-0.323	Destabilizing	0.499	N	0.519	neutral	None	None	None	None	N
T/W	0.8142	likely_pathogenic	0.7368	pathogenic	-0.692	Destabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
T/Y	0.5594	ambiguous	0.4686	ambiguous	-0.469	Destabilizing	0.99	D	0.802	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.