TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5833	17722;17723;17724	chr2:178731168;178731167;178731166	chr2:179595895;179595894;179595893
N2AB	5516	16771;16772;16773	chr2:178731168;178731167;178731166	chr2:179595895;179595894;179595893
N2A	4589	13990;13991;13992	chr2:178731168;178731167;178731166	chr2:179595895;179595894;179595893
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-42
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5335
• 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
D/G	rs1340894070	-0.295	0.91	D	0.512	0.269	0.299086750705	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
D/G	rs1340894070	-0.295	0.91	D	0.512	0.269	0.299086750705	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	0	8.51677E-04	0	0	0	None	0	0	0	0	0
D/G	rs1340894070	-0.295	0.91	D	0.512	0.269	0.299086750705	gnomAD-4.0.0	1.92212E-05	None	None	None	None	N	None	0	2.5428E-04	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
D/A	0.2889	likely_benign	0.2982	benign	-0.296	Destabilizing	0.835	D	0.509	neutral	N	0.469045351	None	None	N
D/C	0.8322	likely_pathogenic	0.8779	pathogenic	-0.016	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
D/E	0.3368	likely_benign	0.3248	benign	-0.31	Destabilizing	0.91	D	0.466	neutral	N	0.423406275	None	None	N
D/F	0.7908	likely_pathogenic	0.797	pathogenic	-0.133	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
D/G	0.387	ambiguous	0.4417	ambiguous	-0.504	Destabilizing	0.91	D	0.512	neutral	D	0.529421806	None	None	N
D/H	0.4576	ambiguous	0.4577	ambiguous	0.061	Stabilizing	0.994	D	0.559	neutral	N	0.492423643	None	None	N
D/I	0.6067	likely_pathogenic	0.61	pathogenic	0.209	Stabilizing	0.996	D	0.631	neutral	None	None	None	None	N
D/K	0.6624	likely_pathogenic	0.6781	pathogenic	0.381	Stabilizing	0.97	D	0.515	neutral	None	None	None	None	N
D/L	0.6374	likely_pathogenic	0.6348	pathogenic	0.209	Stabilizing	0.996	D	0.538	neutral	None	None	None	None	N
D/M	0.7836	likely_pathogenic	0.7941	pathogenic	0.305	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
D/N	0.1494	likely_benign	0.1573	benign	-0.048	Destabilizing	0.248	N	0.224	neutral	N	0.462100736	None	None	N
D/P	0.8863	likely_pathogenic	0.895	pathogenic	0.063	Stabilizing	0.996	D	0.547	neutral	None	None	None	None	N
D/Q	0.5987	likely_pathogenic	0.5953	pathogenic	0.003	Stabilizing	0.996	D	0.473	neutral	None	None	None	None	N
D/R	0.6546	likely_pathogenic	0.6661	pathogenic	0.563	Stabilizing	0.996	D	0.601	neutral	None	None	None	None	N
D/S	0.1887	likely_benign	0.2006	benign	-0.132	Destabilizing	0.348	N	0.125	neutral	None	None	None	None	N
D/T	0.3475	ambiguous	0.3695	ambiguous	0.039	Stabilizing	0.942	D	0.494	neutral	None	None	None	None	N
D/V	0.3773	ambiguous	0.3916	ambiguous	0.063	Stabilizing	0.994	D	0.567	neutral	N	0.448976723	None	None	N
D/W	0.9513	likely_pathogenic	0.9532	pathogenic	0.036	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
D/Y	0.4037	ambiguous	0.4231	ambiguous	0.12	Stabilizing	0.998	D	0.635	neutral	N	0.486671107	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.