TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30768	92527;92528;92529	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
N2AB	29127	87604;87605;87606	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
N2A	28200	84823;84824;84825	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
N2B	21703	65332;65333;65334	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
Novex-1	21828	65707;65708;65709	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
Novex-2	21895	65908;65909;65910	chr2:178549324;178549323;178549322	chr2:179414051;179414050;179414049
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: Fn3-112
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4066
• 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/N	None	None	0.999	N	0.686	0.375	0.202949470691	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/T	None	None	0.999	N	0.735	0.322	0.31501682445	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	2.51915E-05	None	0	0	0	0	1.65645E-05

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	0.7797	likely_pathogenic	0.7529	pathogenic	-0.159	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
K/C	0.915	likely_pathogenic	0.9085	pathogenic	-0.519	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.9335	likely_pathogenic	0.9188	pathogenic	0.042	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/E	0.6556	likely_pathogenic	0.6237	pathogenic	0.127	Stabilizing	0.996	D	0.481	neutral	N	0.495329796	None	None	N
K/F	0.9782	likely_pathogenic	0.9742	pathogenic	0.008	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/G	0.849	likely_pathogenic	0.823	pathogenic	-0.458	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/H	0.5927	likely_pathogenic	0.5721	pathogenic	-0.61	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/I	0.874	likely_pathogenic	0.8674	pathogenic	0.582	Stabilizing	1.0	D	0.734	prob.delet.	D	0.524964844	None	None	N
K/L	0.7821	likely_pathogenic	0.7697	pathogenic	0.582	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/M	0.6912	likely_pathogenic	0.6796	pathogenic	0.096	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/N	0.8562	likely_pathogenic	0.8328	pathogenic	-0.299	Destabilizing	0.999	D	0.686	prob.neutral	N	0.475456935	None	None	N
K/P	0.7419	likely_pathogenic	0.6922	pathogenic	0.365	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/Q	0.3331	likely_benign	0.3248	benign	-0.314	Destabilizing	0.999	D	0.667	neutral	N	0.465074908	None	None	N
K/R	0.0841	likely_benign	0.0836	benign	-0.316	Destabilizing	0.64	D	0.421	neutral	N	0.428763661	None	None	N
K/S	0.8373	likely_pathogenic	0.8172	pathogenic	-0.802	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
K/T	0.5734	likely_pathogenic	0.5487	ambiguous	-0.534	Destabilizing	0.999	D	0.735	prob.delet.	N	0.499719683	None	None	N
K/V	0.8152	likely_pathogenic	0.8015	pathogenic	0.365	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/W	0.9403	likely_pathogenic	0.9362	pathogenic	0.01	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.9217	likely_pathogenic	0.9122	pathogenic	0.324	Stabilizing	1.0	D	0.741	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.