TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17166	51721;51722;51723	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
N2AB	15525	46798;46799;46800	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
N2A	14598	44017;44018;44019	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
N2B	8101	24526;24527;24528	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
Novex-1	8226	24901;24902;24903	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
Novex-2	8293	25102;25103;25104	chr2:178609927;178609926;178609925	chr2:179474654;179474653;179474652
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: Fn3-13
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0909
• 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/V	None	None	0.018	N	0.355	0.086	0.437100570223	gnomAD-4.0.0	1.59299E-06	None	None	None	None	N	None	0	2.28739E-05	None	0	0	None	0	0	0	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	0.971	likely_pathogenic	0.9704	pathogenic	-2.79	Highly Destabilizing	0.207	N	0.584	neutral	None	None	None	None	N
I/C	0.9734	likely_pathogenic	0.9727	pathogenic	-2.049	Highly Destabilizing	0.932	D	0.741	deleterious	None	None	None	None	N
I/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.57	Highly Destabilizing	0.932	D	0.811	deleterious	None	None	None	None	N
I/E	0.9991	likely_pathogenic	0.999	pathogenic	-3.261	Highly Destabilizing	0.818	D	0.78	deleterious	None	None	None	None	N
I/F	0.7983	likely_pathogenic	0.8006	pathogenic	-1.579	Destabilizing	0.193	N	0.587	neutral	N	0.521308463	None	None	N
I/G	0.998	likely_pathogenic	0.9978	pathogenic	-3.368	Highly Destabilizing	0.818	D	0.774	deleterious	None	None	None	None	N
I/H	0.9988	likely_pathogenic	0.9988	pathogenic	-3.115	Highly Destabilizing	0.981	D	0.823	deleterious	None	None	None	None	N
I/K	0.9979	likely_pathogenic	0.9979	pathogenic	-2.14	Highly Destabilizing	0.563	D	0.777	deleterious	None	None	None	None	N
I/L	0.1742	likely_benign	0.2005	benign	-1.046	Destabilizing	None	N	0.181	neutral	N	0.326470721	None	None	N
I/M	0.3918	ambiguous	0.4139	ambiguous	-1.303	Destabilizing	0.627	D	0.629	neutral	N	0.493911218	None	None	N
I/N	0.9975	likely_pathogenic	0.9971	pathogenic	-2.816	Highly Destabilizing	0.912	D	0.822	deleterious	N	0.491563408	None	None	N
I/P	0.9988	likely_pathogenic	0.9983	pathogenic	-1.62	Destabilizing	0.932	D	0.821	deleterious	None	None	None	None	N
I/Q	0.9981	likely_pathogenic	0.998	pathogenic	-2.473	Highly Destabilizing	0.932	D	0.823	deleterious	None	None	None	None	N
I/R	0.9968	likely_pathogenic	0.9966	pathogenic	-2.165	Highly Destabilizing	0.818	D	0.806	deleterious	None	None	None	None	N
I/S	0.9959	likely_pathogenic	0.9956	pathogenic	-3.318	Highly Destabilizing	0.492	N	0.703	prob.neutral	N	0.491309918	None	None	N
I/T	0.9856	likely_pathogenic	0.9856	pathogenic	-2.86	Highly Destabilizing	0.324	N	0.647	neutral	N	0.491309918	None	None	N
I/V	0.1098	likely_benign	0.108	benign	-1.62	Destabilizing	0.018	N	0.355	neutral	N	0.400320693	None	None	N
I/W	0.9977	likely_pathogenic	0.9978	pathogenic	-2.053	Highly Destabilizing	0.981	D	0.816	deleterious	None	None	None	None	N
I/Y	0.991	likely_pathogenic	0.9909	pathogenic	-1.865	Destabilizing	0.818	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.