TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5952	18079;18080;18081	chr2:178730679;178730678;178730677	chr2:179595406;179595405;179595404
N2AB	5635	17128;17129;17130	chr2:178730679;178730678;178730677	chr2:179595406;179595405;179595404
N2A	4708	14347;14348;14349	chr2:178730679;178730678;178730677	chr2:179595406;179595405;179595404
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-43
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.0983
• 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
W/R	None	None	0.928	D	0.874	0.889	0.937825855988	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85892E-06	0	0
W/S	rs2080292615	None	0.864	D	0.867	0.885	0.967651819318	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
W/S	rs2080292615	None	0.864	D	0.867	0.885	0.967651819318	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	2.41406E-05	0	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
W/A	0.9988	likely_pathogenic	0.9976	pathogenic	-2.516	Highly Destabilizing	0.547	D	0.83	deleterious	None	None	None	None	N
W/C	0.9993	likely_pathogenic	0.9987	pathogenic	-0.995	Destabilizing	0.98	D	0.832	deleterious	D	0.719084813	None	None	N
W/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.163	Highly Destabilizing	0.945	D	0.862	deleterious	None	None	None	None	N
W/E	0.9998	likely_pathogenic	0.9997	pathogenic	-3.029	Highly Destabilizing	0.945	D	0.869	deleterious	None	None	None	None	N
W/F	0.823	likely_pathogenic	0.7811	pathogenic	-1.597	Destabilizing	0.894	D	0.767	deleterious	None	None	None	None	N
W/G	0.9925	likely_pathogenic	0.9883	pathogenic	-2.766	Highly Destabilizing	0.928	D	0.825	deleterious	D	0.718883009	None	None	N
W/H	0.9989	likely_pathogenic	0.9981	pathogenic	-2.262	Highly Destabilizing	0.995	D	0.836	deleterious	None	None	None	None	N
W/I	0.9913	likely_pathogenic	0.9847	pathogenic	-1.571	Destabilizing	0.593	D	0.84	deleterious	None	None	None	None	N
W/K	0.9999	likely_pathogenic	0.9999	pathogenic	-2.107	Highly Destabilizing	0.945	D	0.869	deleterious	None	None	None	None	N
W/L	0.9771	likely_pathogenic	0.9643	pathogenic	-1.571	Destabilizing	0.477	N	0.812	deleterious	D	0.718883009	None	None	N
W/M	0.9962	likely_pathogenic	0.9937	pathogenic	-1.013	Destabilizing	0.97	D	0.781	deleterious	None	None	None	None	N
W/N	0.9997	likely_pathogenic	0.9995	pathogenic	-2.877	Highly Destabilizing	0.981	D	0.876	deleterious	None	None	None	None	N
W/P	0.9997	likely_pathogenic	0.9995	pathogenic	-1.915	Destabilizing	0.981	D	0.873	deleterious	None	None	None	None	N
W/Q	0.9999	likely_pathogenic	0.9998	pathogenic	-2.606	Highly Destabilizing	0.981	D	0.861	deleterious	None	None	None	None	N
W/R	0.9998	likely_pathogenic	0.9997	pathogenic	-2.197	Highly Destabilizing	0.928	D	0.874	deleterious	D	0.719084813	None	None	N
W/S	0.9987	likely_pathogenic	0.9975	pathogenic	-2.899	Highly Destabilizing	0.864	D	0.867	deleterious	D	0.719084813	None	None	N
W/T	0.9989	likely_pathogenic	0.9978	pathogenic	-2.681	Highly Destabilizing	0.809	D	0.821	deleterious	None	None	None	None	N
W/V	0.9936	likely_pathogenic	0.9885	pathogenic	-1.915	Destabilizing	0.017	N	0.752	deleterious	None	None	None	None	N
W/Y	0.9582	likely_pathogenic	0.9411	pathogenic	-1.441	Destabilizing	0.945	D	0.762	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.