TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26939	81040;81041;81042	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
N2AB	25298	76117;76118;76119	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
N2A	24371	73336;73337;73338	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
N2B	17874	53845;53846;53847	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
Novex-1	17999	54220;54221;54222	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
Novex-2	18066	54421;54422;54423	chr2:178565317;178565316;178565315	chr2:179430044;179430043;179430042
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-139
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1804
• 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/N	rs1705331466	None	0.975	D	0.853	0.827	0.921599369569	gnomAD-4.0.0	1.36853E-06	None	None	None	None	N	None	0	0	None	0	5.03931E-05	None	0	0	0	0	0
I/T	rs1705331466	None	0.645	D	0.763	0.825	0.839350010842	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/T	rs1705331466	None	0.645	D	0.763	0.825	0.839350010842	gnomAD-4.0.0	3.71873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08619E-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	0.9603	likely_pathogenic	0.9409	pathogenic	-3.069	Highly Destabilizing	0.547	D	0.691	prob.neutral	None	None	None	None	N
I/C	0.9134	likely_pathogenic	0.8835	pathogenic	-2.674	Highly Destabilizing	0.985	D	0.76	deleterious	None	None	None	None	N
I/D	0.9977	likely_pathogenic	0.9968	pathogenic	-3.57	Highly Destabilizing	0.981	D	0.854	deleterious	None	None	None	None	N
I/E	0.9927	likely_pathogenic	0.9898	pathogenic	-3.345	Highly Destabilizing	0.945	D	0.859	deleterious	None	None	None	None	N
I/F	0.3561	ambiguous	0.3246	benign	-1.898	Destabilizing	0.864	D	0.74	deleterious	D	0.583865081	None	None	N
I/G	0.9902	likely_pathogenic	0.9855	pathogenic	-3.612	Highly Destabilizing	0.945	D	0.863	deleterious	None	None	None	None	N
I/H	0.9743	likely_pathogenic	0.9647	pathogenic	-2.939	Highly Destabilizing	0.995	D	0.83	deleterious	None	None	None	None	N
I/K	0.9689	likely_pathogenic	0.9591	pathogenic	-2.588	Highly Destabilizing	0.945	D	0.857	deleterious	None	None	None	None	N
I/L	0.1951	likely_benign	0.1802	benign	-1.485	Destabilizing	0.141	N	0.462	neutral	D	0.562264845	None	None	N
I/M	0.2246	likely_benign	0.2004	benign	-1.596	Destabilizing	0.864	D	0.699	prob.neutral	D	0.608999584	None	None	N
I/N	0.9643	likely_pathogenic	0.9553	pathogenic	-2.993	Highly Destabilizing	0.975	D	0.853	deleterious	D	0.661488438	None	None	N
I/P	0.9966	likely_pathogenic	0.9952	pathogenic	-1.997	Destabilizing	0.981	D	0.846	deleterious	None	None	None	None	N
I/Q	0.9715	likely_pathogenic	0.9623	pathogenic	-2.867	Highly Destabilizing	0.981	D	0.853	deleterious	None	None	None	None	N
I/R	0.9494	likely_pathogenic	0.9372	pathogenic	-2.16	Highly Destabilizing	0.945	D	0.856	deleterious	None	None	None	None	N
I/S	0.9604	likely_pathogenic	0.9453	pathogenic	-3.686	Highly Destabilizing	0.864	D	0.839	deleterious	D	0.635950326	None	None	N
I/T	0.9541	likely_pathogenic	0.931	pathogenic	-3.315	Highly Destabilizing	0.645	D	0.763	deleterious	D	0.661084829	None	None	N
I/V	0.1605	likely_benign	0.1241	benign	-1.997	Destabilizing	0.002	N	0.279	neutral	D	0.56197196	None	None	N
I/W	0.9379	likely_pathogenic	0.9248	pathogenic	-2.255	Highly Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	N
I/Y	0.8907	likely_pathogenic	0.8593	pathogenic	-2.063	Highly Destabilizing	0.945	D	0.753	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.