TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31675	95248;95249;95250	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
N2AB	30034	90325;90326;90327	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
N2A	29107	87544;87545;87546	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
N2B	22610	68053;68054;68055	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
Novex-1	22735	68428;68429;68430	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
Novex-2	22802	68629;68630;68631	chr2:178546308;178546307;178546306	chr2:179411035;179411034;179411033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-152
• Domain position: 55
• Structural Position: 140
• Q(SASA): 0.156
• 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
I/T	None	None	0.939	D	0.749	0.853	0.837465136938	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85832E-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
I/A	0.954	likely_pathogenic	0.9662	pathogenic	-3.045	Highly Destabilizing	0.91	D	0.667	neutral	None	None	None	None	N
I/C	0.9213	likely_pathogenic	0.9353	pathogenic	-2.501	Highly Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
I/D	0.9972	likely_pathogenic	0.9976	pathogenic	-3.555	Highly Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
I/E	0.9899	likely_pathogenic	0.9902	pathogenic	-3.322	Highly Destabilizing	0.993	D	0.854	deleterious	None	None	None	None	N
I/F	0.4797	ambiguous	0.5134	ambiguous	-1.911	Destabilizing	0.991	D	0.72	prob.delet.	D	0.590597856	None	None	N
I/G	0.9902	likely_pathogenic	0.9921	pathogenic	-3.612	Highly Destabilizing	0.993	D	0.855	deleterious	None	None	None	None	N
I/H	0.971	likely_pathogenic	0.9728	pathogenic	-3.024	Highly Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
I/K	0.9665	likely_pathogenic	0.9647	pathogenic	-2.594	Highly Destabilizing	0.993	D	0.853	deleterious	None	None	None	None	N
I/L	0.2436	likely_benign	0.2542	benign	-1.388	Destabilizing	0.58	D	0.447	neutral	D	0.579302666	None	None	N
I/M	0.2959	likely_benign	0.3218	benign	-1.339	Destabilizing	0.991	D	0.685	prob.neutral	D	0.619446994	None	None	N
I/N	0.9439	likely_pathogenic	0.9497	pathogenic	-2.99	Highly Destabilizing	0.997	D	0.856	deleterious	D	0.620859624	None	None	N
I/P	0.9959	likely_pathogenic	0.9967	pathogenic	-1.924	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
I/Q	0.9672	likely_pathogenic	0.9666	pathogenic	-2.847	Highly Destabilizing	0.998	D	0.862	deleterious	None	None	None	None	N
I/R	0.9491	likely_pathogenic	0.9484	pathogenic	-2.185	Highly Destabilizing	0.998	D	0.861	deleterious	None	None	None	None	N
I/S	0.9499	likely_pathogenic	0.9595	pathogenic	-3.689	Highly Destabilizing	0.991	D	0.839	deleterious	D	0.620859624	None	None	N
I/T	0.9378	likely_pathogenic	0.9536	pathogenic	-3.307	Highly Destabilizing	0.939	D	0.749	deleterious	D	0.620456015	None	None	N
I/V	0.1208	likely_benign	0.1452	benign	-1.924	Destabilizing	0.02	N	0.249	neutral	D	0.572148192	None	None	N
I/W	0.9617	likely_pathogenic	0.966	pathogenic	-2.332	Highly Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
I/Y	0.9116	likely_pathogenic	0.913	pathogenic	-2.113	Highly Destabilizing	0.998	D	0.745	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.