TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2579	7960;7961;7962	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
N2AB	2579	7960;7961;7962	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
N2A	2579	7960;7961;7962	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
N2B	2533	7822;7823;7824	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
Novex-1	2533	7822;7823;7824	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
Novex-2	2533	7822;7823;7824	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954
Novex-3	2579	7960;7961;7962	chr2:178773229;178773228;178773227	chr2:179637956;179637955;179637954

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-15
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.2556
• 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/E	None	None	0.41	N	0.382	0.325	0.26547132957	gnomAD-4.0.0	2.05255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7987E-06	1.15964E-05	0
K/R	rs1222416655	-0.502	0.581	N	0.423	0.303	0.376745185316	gnomAD-2.1.1	4E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs1222416655	-0.502	0.581	N	0.423	0.303	0.376745185316	gnomAD-4.0.0	1.36836E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15961E-05	1.65629E-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
K/A	0.5553	ambiguous	0.4905	ambiguous	-0.356	Destabilizing	0.648	D	0.536	neutral	None	None	None	None	N
K/C	0.7871	likely_pathogenic	0.7716	pathogenic	-0.442	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	N
K/D	0.7669	likely_pathogenic	0.6793	pathogenic	0.295	Stabilizing	0.764	D	0.603	neutral	None	None	None	None	N
K/E	0.2768	likely_benign	0.2198	benign	0.373	Stabilizing	0.41	N	0.382	neutral	N	0.499488609	None	None	N
K/F	0.8664	likely_pathogenic	0.8381	pathogenic	-0.209	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
K/G	0.7566	likely_pathogenic	0.6916	pathogenic	-0.671	Destabilizing	0.48	N	0.55	neutral	None	None	None	None	N
K/H	0.3427	ambiguous	0.3238	benign	-0.968	Destabilizing	0.961	D	0.674	neutral	None	None	None	None	N
K/I	0.4124	ambiguous	0.3463	ambiguous	0.432	Stabilizing	0.908	D	0.749	deleterious	N	0.517292166	None	None	N
K/L	0.4661	ambiguous	0.4134	ambiguous	0.432	Stabilizing	0.866	D	0.615	neutral	None	None	None	None	N
K/M	0.3153	likely_benign	0.2704	benign	0.243	Stabilizing	0.993	D	0.667	neutral	None	None	None	None	N
K/N	0.5407	ambiguous	0.4384	ambiguous	-0.078	Destabilizing	0.01	N	0.261	neutral	D	0.535257814	None	None	N
K/P	0.9809	likely_pathogenic	0.969	pathogenic	0.2	Stabilizing	0.929	D	0.706	prob.neutral	None	None	None	None	N
K/Q	0.1598	likely_benign	0.1466	benign	-0.184	Destabilizing	0.83	D	0.565	neutral	N	0.509080442	None	None	N
K/R	0.0929	likely_benign	0.0929	benign	-0.314	Destabilizing	0.581	D	0.423	neutral	N	0.491361187	None	None	N
K/S	0.5713	likely_pathogenic	0.4902	ambiguous	-0.76	Destabilizing	0.48	N	0.417	neutral	None	None	None	None	N
K/T	0.2305	likely_benign	0.1863	benign	-0.485	Destabilizing	0.709	D	0.629	neutral	N	0.513138986	None	None	N
K/V	0.4088	ambiguous	0.3524	ambiguous	0.2	Stabilizing	0.929	D	0.708	prob.delet.	None	None	None	None	N
K/W	0.872	likely_pathogenic	0.8592	pathogenic	-0.091	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.7616	likely_pathogenic	0.7232	pathogenic	0.216	Stabilizing	0.976	D	0.713	prob.delet.	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.