TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24710	74353;74354;74355	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
N2AB	23069	69430;69431;69432	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
N2A	22142	66649;66650;66651	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
N2B	15645	47158;47159;47160	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
Novex-1	15770	47533;47534;47535	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
Novex-2	15837	47734;47735;47736	chr2:178572004;178572003;178572002	chr2:179436731;179436730;179436729
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: Fn3-67
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.3244
• 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/T	None	None	0.997	N	0.646	0.515	0.457377140028	gnomAD-4.0.0	1.59243E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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
K/A	0.7572	likely_pathogenic	0.7339	pathogenic	-0.442	Destabilizing	0.998	D	0.701	prob.delet.	None	None	None	None	N
K/C	0.8991	likely_pathogenic	0.8952	pathogenic	-0.511	Destabilizing	1.0	D	0.724	deleterious	None	None	None	None	N
K/D	0.9194	likely_pathogenic	0.9144	pathogenic	-0.031	Destabilizing	0.999	D	0.694	prob.delet.	None	None	None	None	N
K/E	0.4409	ambiguous	0.4365	ambiguous	0.034	Stabilizing	0.99	D	0.711	prob.delet.	N	0.517550508	None	None	N
K/F	0.9781	likely_pathogenic	0.9738	pathogenic	-0.365	Destabilizing	1.0	D	0.697	prob.delet.	None	None	None	None	N
K/G	0.8352	likely_pathogenic	0.8299	pathogenic	-0.755	Destabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
K/H	0.6089	likely_pathogenic	0.5924	pathogenic	-1.151	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
K/I	0.8311	likely_pathogenic	0.8089	pathogenic	0.339	Stabilizing	0.972	D	0.72	deleterious	N	0.479340821	None	None	N
K/L	0.8083	likely_pathogenic	0.7948	pathogenic	0.339	Stabilizing	0.978	D	0.663	prob.neutral	None	None	None	None	N
K/M	0.6308	likely_pathogenic	0.6105	pathogenic	0.298	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	N
K/N	0.8331	likely_pathogenic	0.8125	pathogenic	-0.253	Destabilizing	0.999	D	0.701	prob.delet.	N	0.502053432	None	None	N
K/P	0.9898	likely_pathogenic	0.9901	pathogenic	0.109	Stabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
K/Q	0.2566	likely_benign	0.2467	benign	-0.424	Destabilizing	0.993	D	0.733	deleterious	N	0.467451083	None	None	N
K/R	0.093	likely_benign	0.0908	benign	-0.462	Destabilizing	0.984	D	0.65	prob.neutral	N	0.469954136	None	None	N
K/S	0.7819	likely_pathogenic	0.7712	pathogenic	-0.908	Destabilizing	0.998	D	0.735	deleterious	None	None	None	None	N
K/T	0.4952	ambiguous	0.4635	ambiguous	-0.652	Destabilizing	0.997	D	0.646	neutral	N	0.477365811	None	None	N
K/V	0.7097	likely_pathogenic	0.689	pathogenic	0.109	Stabilizing	0.984	D	0.707	prob.delet.	None	None	None	None	N
K/W	0.9561	likely_pathogenic	0.9504	pathogenic	-0.236	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/Y	0.9305	likely_pathogenic	0.9214	pathogenic	0.078	Stabilizing	0.996	D	0.723	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.