TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15496	46711;46712;46713	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
N2AB	13855	41788;41789;41790	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
N2A	12928	39007;39008;39009	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
N2B	6431	19516;19517;19518	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
Novex-1	6556	19891;19892;19893	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
Novex-2	6623	20092;20093;20094	chr2:178619831;178619830;178619829	chr2:179484558;179484557;179484556
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-107
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.547
• 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/V	rs755301020	None	1.0	N	0.85	0.606	0.741726271847	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.5446	ambiguous	0.4845	ambiguous	-0.408	Destabilizing	1.0	D	0.807	deleterious	D	0.582904669	None	None	N
D/C	0.9332	likely_pathogenic	0.9273	pathogenic	-0.067	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/E	0.5228	ambiguous	0.4769	ambiguous	-0.507	Destabilizing	1.0	D	0.445	neutral	N	0.500249582	None	None	N
D/F	0.9506	likely_pathogenic	0.9436	pathogenic	-0.329	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
D/G	0.5817	likely_pathogenic	0.5239	ambiguous	-0.662	Destabilizing	1.0	D	0.783	deleterious	D	0.587529184	None	None	N
D/H	0.7601	likely_pathogenic	0.7224	pathogenic	-0.45	Destabilizing	1.0	D	0.762	deleterious	D	0.588100865	None	None	N
D/I	0.8922	likely_pathogenic	0.8881	pathogenic	0.227	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/K	0.8572	likely_pathogenic	0.838	pathogenic	-0.117	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
D/L	0.8879	likely_pathogenic	0.8675	pathogenic	0.227	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
D/M	0.9384	likely_pathogenic	0.9264	pathogenic	0.512	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
D/N	0.2642	likely_benign	0.2352	benign	-0.366	Destabilizing	1.0	D	0.673	neutral	N	0.508512571	None	None	N
D/P	0.8811	likely_pathogenic	0.849	pathogenic	0.039	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/Q	0.8046	likely_pathogenic	0.7682	pathogenic	-0.305	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
D/R	0.8706	likely_pathogenic	0.849	pathogenic	0.044	Stabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
D/S	0.3049	likely_benign	0.2704	benign	-0.528	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/T	0.6091	likely_pathogenic	0.5696	pathogenic	-0.338	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/V	0.7316	likely_pathogenic	0.7015	pathogenic	0.039	Stabilizing	1.0	D	0.85	deleterious	N	0.502860038	None	None	N
D/W	0.9869	likely_pathogenic	0.9858	pathogenic	-0.217	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/Y	0.7338	likely_pathogenic	0.697	pathogenic	-0.117	Destabilizing	1.0	D	0.83	deleterious	D	0.589039986	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.