TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18906	56941;56942;56943	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
N2AB	17265	52018;52019;52020	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
N2A	16338	49237;49238;49239	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
N2B	9841	29746;29747;29748	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
Novex-1	9966	30121;30122;30123	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
Novex-2	10033	30322;30323;30324	chr2:178598994;178598993;178598992	chr2:179463721;179463720;179463719
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-25
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5296
• Predicted PPI site: I

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
E/K	rs1263513465	-0.056	0.978	N	0.547	0.415	0.316788114976	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
E/K	rs1263513465	-0.056	0.978	N	0.547	0.415	0.316788114976	gnomAD-4.0.0	6.16957E-06	None	None	None	None	I	None	0	2.24699E-05	None	0	0	None	0	0	7.2041E-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
E/A	0.3151	likely_benign	0.2385	benign	-0.393	Destabilizing	0.989	D	0.627	neutral	N	0.4774244	None	None	I
E/C	0.9109	likely_pathogenic	0.8429	pathogenic	-0.112	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
E/D	0.238	likely_benign	0.192	benign	-0.489	Destabilizing	0.054	N	0.246	neutral	N	0.449891082	None	None	I
E/F	0.917	likely_pathogenic	0.844	pathogenic	-0.165	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
E/G	0.3372	likely_benign	0.2628	benign	-0.636	Destabilizing	0.978	D	0.631	neutral	N	0.504515001	None	None	I
E/H	0.7392	likely_pathogenic	0.5816	pathogenic	-0.077	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
E/I	0.6573	likely_pathogenic	0.519	ambiguous	0.225	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	I
E/K	0.3738	ambiguous	0.2438	benign	0.139	Stabilizing	0.978	D	0.547	neutral	N	0.424877994	None	None	I
E/L	0.6406	likely_pathogenic	0.5035	ambiguous	0.225	Stabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	I
E/M	0.6439	likely_pathogenic	0.5363	ambiguous	0.324	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
E/N	0.4387	ambiguous	0.3041	benign	-0.178	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	I
E/P	0.9289	likely_pathogenic	0.8915	pathogenic	0.04	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
E/Q	0.2591	likely_benign	0.185	benign	-0.12	Destabilizing	0.997	D	0.633	neutral	N	0.456625053	None	None	I
E/R	0.5083	ambiguous	0.3601	ambiguous	0.376	Stabilizing	0.998	D	0.633	neutral	None	None	None	None	I
E/S	0.3947	ambiguous	0.2991	benign	-0.371	Destabilizing	0.983	D	0.554	neutral	None	None	None	None	I
E/T	0.4107	ambiguous	0.3127	benign	-0.175	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	I
E/V	0.4373	ambiguous	0.3232	benign	0.04	Stabilizing	0.999	D	0.69	prob.neutral	N	0.504341642	None	None	I
E/W	0.9609	likely_pathogenic	0.9271	pathogenic	0.004	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/Y	0.8392	likely_pathogenic	0.7103	pathogenic	0.082	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I

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.