TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9720	29383;29384;29385	chr2:178706716;178706715;178706714	chr2:179571443;179571442;179571441
N2AB	9403	28432;28433;28434	chr2:178706716;178706715;178706714	chr2:179571443;179571442;179571441
N2A	8476	25651;25652;25653	chr2:178706716;178706715;178706714	chr2:179571443;179571442;179571441
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-83
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4837
• 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
K/E	rs780071353	0.335	0.41	None	0.467	0.305	0.294561560033	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs780071353	0.335	0.41	None	0.467	0.305	0.294561560033	gnomAD-4.0.0	8.00869E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.44115E-05	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
K/A	0.8555	likely_pathogenic	0.6806	pathogenic	-0.712	Destabilizing	0.648	D	0.565	neutral	None	None	None	None	I
K/C	0.9464	likely_pathogenic	0.9049	pathogenic	-0.898	Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	I
K/D	0.9718	likely_pathogenic	0.9102	pathogenic	-0.457	Destabilizing	0.866	D	0.745	deleterious	None	None	None	None	I
K/E	0.6436	likely_pathogenic	0.3708	ambiguous	-0.362	Destabilizing	0.41	N	0.467	neutral	None	None	None	None	I
K/F	0.9789	likely_pathogenic	0.9515	pathogenic	-0.59	Destabilizing	0.98	D	0.755	deleterious	None	None	None	None	I
K/G	0.9536	likely_pathogenic	0.8607	pathogenic	-1.053	Destabilizing	0.866	D	0.685	prob.neutral	None	None	None	None	I
K/H	0.6559	likely_pathogenic	0.5218	ambiguous	-1.416	Destabilizing	0.98	D	0.734	prob.delet.	None	None	None	None	I
K/I	0.7774	likely_pathogenic	0.6579	pathogenic	0.162	Stabilizing	0.908	D	0.769	deleterious	None	None	None	None	I
K/L	0.8225	likely_pathogenic	0.6865	pathogenic	0.162	Stabilizing	0.866	D	0.685	prob.neutral	None	None	None	None	I
K/M	0.6544	likely_pathogenic	0.4877	ambiguous	0.162	Stabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	I
K/N	0.8866	likely_pathogenic	0.7573	pathogenic	-0.653	Destabilizing	0.83	D	0.657	neutral	None	None	None	None	I
K/P	0.9975	likely_pathogenic	0.9875	pathogenic	-0.1	Destabilizing	0.929	D	0.744	deleterious	None	None	None	None	I
K/Q	0.3817	ambiguous	0.2504	benign	-0.833	Destabilizing	0.83	D	0.644	neutral	None	None	None	None	I
K/R	0.1091	likely_benign	0.0941	benign	-0.641	Destabilizing	0.01	N	0.351	neutral	None	None	None	None	I
K/S	0.8844	likely_pathogenic	0.743	pathogenic	-1.338	Destabilizing	0.648	D	0.533	neutral	None	None	None	None	I
K/T	0.5559	ambiguous	0.3615	ambiguous	-1.044	Destabilizing	0.83	D	0.707	prob.neutral	None	None	None	None	I
K/V	0.7003	likely_pathogenic	0.564	ambiguous	-0.1	Destabilizing	0.866	D	0.738	prob.delet.	None	None	None	None	I
K/W	0.9716	likely_pathogenic	0.9353	pathogenic	-0.437	Destabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	I
K/Y	0.9371	likely_pathogenic	0.8866	pathogenic	-0.102	Destabilizing	0.929	D	0.759	deleterious	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.