TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14422	43489;43490;43491	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
N2AB	12781	38566;38567;38568	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
N2A	11854	35785;35786;35787	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
N2B	5357	16294;16295;16296	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
Novex-1	5482	16669;16670;16671	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
Novex-2	5549	16870;16871;16872	chr2:178632742;178632741;178632740	chr2:179497469;179497468;179497467
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-95
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.7106
• 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
K/E	rs1576692871	None	0.999	D	0.747	0.37	0.390220360785	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	0	2.28707E-05	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
K/A	0.6252	likely_pathogenic	0.6278	pathogenic	0.077	Stabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
K/C	0.9261	likely_pathogenic	0.9207	pathogenic	-0.072	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.6357	likely_pathogenic	0.6474	pathogenic	-0.018	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/E	0.2694	likely_benign	0.272	benign	-0.03	Destabilizing	0.999	D	0.747	deleterious	D	0.523546361	None	None	N
K/F	0.9255	likely_pathogenic	0.9248	pathogenic	-0.216	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
K/G	0.4597	ambiguous	0.4881	ambiguous	-0.096	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.5354	ambiguous	0.5189	ambiguous	-0.385	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/I	0.7975	likely_pathogenic	0.7996	pathogenic	0.451	Stabilizing	1.0	D	0.718	prob.delet.	D	0.643698177	None	None	N
K/L	0.6542	likely_pathogenic	0.653	pathogenic	0.451	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/M	0.4309	ambiguous	0.4167	ambiguous	0.313	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/N	0.3981	ambiguous	0.4164	ambiguous	0.38	Stabilizing	1.0	D	0.741	deleterious	D	0.53471352	None	None	N
K/P	0.9645	likely_pathogenic	0.9649	pathogenic	0.353	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/Q	0.2407	likely_benign	0.2382	benign	0.163	Stabilizing	1.0	D	0.751	deleterious	D	0.641370572	None	None	N
K/R	0.1391	likely_benign	0.1285	benign	0.102	Stabilizing	0.999	D	0.731	prob.delet.	D	0.548198286	None	None	N
K/S	0.6065	likely_pathogenic	0.6229	pathogenic	-0.074	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
K/T	0.3849	ambiguous	0.3778	ambiguous	0.05	Stabilizing	1.0	D	0.749	deleterious	D	0.5285522	None	None	N
K/V	0.7639	likely_pathogenic	0.7589	pathogenic	0.353	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.9259	likely_pathogenic	0.915	pathogenic	-0.248	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
K/Y	0.8061	likely_pathogenic	0.8001	pathogenic	0.12	Stabilizing	1.0	D	0.752	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.