TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22517	67774;67775;67776	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
N2AB	20876	62851;62852;62853	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
N2A	19949	60070;60071;60072	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
N2B	13452	40579;40580;40581	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
Novex-1	13577	40954;40955;40956	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
Novex-2	13644	41155;41156;41157	chr2:178579648;178579647;178579646	chr2:179444375;179444374;179444373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-51
• Domain position: 67
• Structural Position: 102
• Q(SASA): 0.2967
• 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
K/R	None	None	0.379	N	0.408	0.106	0.293147016451	gnomAD-4.0.0	2.40078E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62516E-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
K/A	0.3546	ambiguous	0.3516	ambiguous	-0.683	Destabilizing	0.447	N	0.284	neutral	None	None	None	None	N
K/C	0.6193	likely_pathogenic	0.6305	pathogenic	-0.604	Destabilizing	0.992	D	0.565	neutral	None	None	None	None	N
K/D	0.5548	ambiguous	0.5428	ambiguous	0.033	Stabilizing	0.447	N	0.308	neutral	None	None	None	None	N
K/E	0.145	likely_benign	0.1495	benign	0.154	Stabilizing	0.004	N	0.217	neutral	N	0.451640521	None	None	N
K/F	0.7621	likely_pathogenic	0.7925	pathogenic	-0.394	Destabilizing	0.92	D	0.503	neutral	None	None	None	None	N
K/G	0.429	ambiguous	0.4356	ambiguous	-1.034	Destabilizing	0.617	D	0.402	neutral	None	None	None	None	N
K/H	0.3028	likely_benign	0.309	benign	-1.236	Destabilizing	0.012	N	0.347	neutral	None	None	None	None	N
K/I	0.3589	ambiguous	0.3757	ambiguous	0.226	Stabilizing	0.92	D	0.494	neutral	None	None	None	None	N
K/L	0.3604	ambiguous	0.3735	ambiguous	0.226	Stabilizing	0.617	D	0.39	neutral	None	None	None	None	N
K/M	0.2026	likely_benign	0.2143	benign	-0.01	Destabilizing	0.97	D	0.357	neutral	N	0.497508884	None	None	N
K/N	0.3455	ambiguous	0.3539	ambiguous	-0.414	Destabilizing	0.549	D	0.389	neutral	N	0.477384328	None	None	N
K/P	0.9545	likely_pathogenic	0.9552	pathogenic	-0.048	Destabilizing	0.92	D	0.371	neutral	None	None	None	None	N
K/Q	0.1132	likely_benign	0.1145	benign	-0.418	Destabilizing	0.016	N	0.183	neutral	N	0.478923123	None	None	N
K/R	0.0783	likely_benign	0.0801	benign	-0.47	Destabilizing	0.379	N	0.408	neutral	N	0.460836008	None	None	N
K/S	0.3576	ambiguous	0.363	ambiguous	-1.078	Destabilizing	0.447	N	0.343	neutral	None	None	None	None	N
K/T	0.1707	likely_benign	0.1681	benign	-0.742	Destabilizing	0.549	D	0.351	neutral	N	0.440743163	None	None	N
K/V	0.3027	likely_benign	0.3063	benign	-0.048	Destabilizing	0.85	D	0.403	neutral	None	None	None	None	N
K/W	0.7484	likely_pathogenic	0.7925	pathogenic	-0.282	Destabilizing	0.992	D	0.581	neutral	None	None	None	None	N
K/Y	0.6407	likely_pathogenic	0.6632	pathogenic	-0.007	Destabilizing	0.85	D	0.427	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.