TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15357	46294;46295;46296	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
N2AB	13716	41371;41372;41373	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
N2A	12789	38590;38591;38592	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
N2B	6292	19099;19100;19101	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
Novex-1	6417	19474;19475;19476	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
Novex-2	6484	19675;19676;19677	chr2:178620452;178620451;178620450	chr2:179485179;179485178;179485177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-105
• Domain position: 56
• Structural Position: 137
• Q(SASA): 0.1175
• 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
M/I	None	None	None	N	0.231	0.104	0.206339911435	gnomAD-4.0.0	6.84779E-07	None	None	None	None	N	None	0	0	None	0	2.52589E-05	None	0	0	0	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
M/A	0.2454	likely_benign	0.288	benign	-2.867	Highly Destabilizing	None	N	0.447	neutral	None	None	None	None	N
M/C	0.3013	likely_benign	0.35	ambiguous	-2.352	Highly Destabilizing	0.132	N	0.67	neutral	None	None	None	None	N
M/D	0.8044	likely_pathogenic	0.8546	pathogenic	-2.349	Highly Destabilizing	0.002	N	0.626	neutral	None	None	None	None	N
M/E	0.47	ambiguous	0.4725	ambiguous	-2.164	Highly Destabilizing	0.002	N	0.621	neutral	None	None	None	None	N
M/F	0.2175	likely_benign	0.2562	benign	-1.273	Destabilizing	0.018	N	0.497	neutral	None	None	None	None	N
M/G	0.4601	ambiguous	0.518	ambiguous	-3.294	Highly Destabilizing	0.001	N	0.631	neutral	None	None	None	None	N
M/H	0.3526	ambiguous	0.3864	ambiguous	-2.672	Highly Destabilizing	0.132	N	0.671	neutral	None	None	None	None	N
M/I	0.2392	likely_benign	0.2963	benign	-1.636	Destabilizing	None	N	0.231	neutral	N	0.415032104	None	None	N
M/K	0.3956	ambiguous	0.3981	ambiguous	-1.934	Destabilizing	0.001	N	0.554	neutral	N	0.439098665	None	None	N
M/L	0.186	likely_benign	0.2407	benign	-1.636	Destabilizing	None	N	0.291	neutral	N	0.483950755	None	None	N
M/N	0.348	ambiguous	0.3955	ambiguous	-2.107	Highly Destabilizing	0.002	N	0.607	neutral	None	None	None	None	N
M/P	0.9914	likely_pathogenic	0.995	pathogenic	-2.032	Highly Destabilizing	0.009	N	0.6	neutral	None	None	None	None	N
M/Q	0.2556	likely_benign	0.2343	benign	-1.918	Destabilizing	0.009	N	0.481	neutral	None	None	None	None	N
M/R	0.3446	ambiguous	0.3783	ambiguous	-1.727	Destabilizing	0.007	N	0.554	neutral	N	0.434436835	None	None	N
M/S	0.1545	likely_benign	0.1683	benign	-2.71	Highly Destabilizing	None	N	0.347	neutral	None	None	None	None	N
M/T	0.1351	likely_benign	0.1534	benign	-2.422	Highly Destabilizing	None	N	0.346	neutral	N	0.359585083	None	None	N
M/V	0.129	likely_benign	0.1472	benign	-2.032	Highly Destabilizing	None	N	0.356	neutral	N	0.483950755	None	None	N
M/W	0.5184	ambiguous	0.5824	pathogenic	-1.505	Destabilizing	0.316	N	0.642	neutral	None	None	None	None	N
M/Y	0.3194	likely_benign	0.3901	ambiguous	-1.611	Destabilizing	0.018	N	0.63	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.