TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16604	50035;50036;50037	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
N2AB	14963	45112;45113;45114	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
N2A	14036	42331;42332;42333	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
N2B	7539	22840;22841;22842	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
Novex-1	7664	23215;23216;23217	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
Novex-2	7731	23416;23417;23418	chr2:178612911;178612910;178612909	chr2:179477638;179477637;179477636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-8
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.2774
• 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
G/R	rs890124853	None	0.999	N	0.745	0.298	0.585534595853	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.1708	likely_benign	0.2073	benign	-0.39	Destabilizing	0.996	D	0.533	neutral	N	0.464459849	None	None	N
G/C	0.3535	ambiguous	0.3899	ambiguous	-0.895	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/D	0.1365	likely_benign	0.1954	benign	-0.814	Destabilizing	0.996	D	0.698	prob.neutral	None	None	None	None	N
G/E	0.2265	likely_benign	0.3342	benign	-0.965	Destabilizing	0.998	D	0.737	prob.delet.	N	0.457900853	None	None	N
G/F	0.6874	likely_pathogenic	0.7556	pathogenic	-1.011	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/H	0.4439	ambiguous	0.5612	ambiguous	-0.7	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/I	0.431	ambiguous	0.5638	ambiguous	-0.442	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
G/K	0.5075	ambiguous	0.6961	pathogenic	-1.077	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
G/L	0.5683	likely_pathogenic	0.642	pathogenic	-0.442	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
G/M	0.5587	ambiguous	0.6308	pathogenic	-0.481	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/N	0.182	likely_benign	0.2023	benign	-0.681	Destabilizing	0.683	D	0.337	neutral	None	None	None	None	N
G/P	0.8975	likely_pathogenic	0.9344	pathogenic	-0.39	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/Q	0.4218	ambiguous	0.5499	ambiguous	-0.966	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
G/R	0.447	ambiguous	0.6501	pathogenic	-0.592	Destabilizing	0.999	D	0.745	deleterious	N	0.466276134	None	None	N
G/S	0.1267	likely_benign	0.1434	benign	-0.811	Destabilizing	0.994	D	0.547	neutral	None	None	None	None	N
G/T	0.2086	likely_benign	0.2668	benign	-0.895	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
G/V	0.2987	likely_benign	0.4131	ambiguous	-0.39	Destabilizing	1.0	D	0.781	deleterious	N	0.43955598	None	None	N
G/W	0.5633	ambiguous	0.6969	pathogenic	-1.199	Destabilizing	1.0	D	0.738	prob.delet.	D	0.541139035	None	None	N
G/Y	0.4929	ambiguous	0.5916	pathogenic	-0.857	Destabilizing	1.0	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.