TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16874	50845;50846;50847	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
N2AB	15233	45922;45923;45924	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
N2A	14306	43141;43142;43143	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
N2B	7809	23650;23651;23652	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
Novex-1	7934	24025;24026;24027	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
Novex-2	8001	24226;24227;24228	chr2:178611609;178611608;178611607	chr2:179476336;179476335;179476334
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-11
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4333
• 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	None	None	0.999	N	0.575	0.444	0.301455362545	gnomAD-4.0.0	6.84504E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99755E-07	0	0
K/T	None	None	1.0	N	0.797	0.471	0.392395365052	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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	0.6867	likely_pathogenic	0.6494	pathogenic	-0.393	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
K/C	0.8965	likely_pathogenic	0.8628	pathogenic	-0.374	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/D	0.8585	likely_pathogenic	0.8242	pathogenic	-0.098	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
K/E	0.461	ambiguous	0.4058	ambiguous	0.001	Stabilizing	0.999	D	0.575	neutral	N	0.458216615	None	None	N
K/F	0.947	likely_pathogenic	0.9234	pathogenic	-0.081	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/G	0.771	likely_pathogenic	0.7285	pathogenic	-0.731	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/H	0.5222	ambiguous	0.4871	ambiguous	-0.947	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/I	0.6345	likely_pathogenic	0.5793	pathogenic	0.474	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/L	0.5966	likely_pathogenic	0.5352	ambiguous	0.474	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/M	0.4447	ambiguous	0.3902	ambiguous	0.163	Stabilizing	1.0	D	0.781	deleterious	N	0.5164882159999999	None	None	N
K/N	0.5857	likely_pathogenic	0.5488	ambiguous	-0.29	Destabilizing	1.0	D	0.721	prob.delet.	N	0.48394441	None	None	N
K/P	0.9911	likely_pathogenic	0.9862	pathogenic	0.215	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/Q	0.2252	likely_benign	0.2062	benign	-0.311	Destabilizing	1.0	D	0.69	prob.neutral	N	0.477789264	None	None	N
K/R	0.1385	likely_benign	0.1293	benign	-0.472	Destabilizing	0.999	D	0.548	neutral	N	0.483796743	None	None	N
K/S	0.6862	likely_pathogenic	0.6503	pathogenic	-0.833	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
K/T	0.4028	ambiguous	0.3574	ambiguous	-0.539	Destabilizing	1.0	D	0.797	deleterious	N	0.474332723	None	None	N
K/V	0.6021	likely_pathogenic	0.5492	ambiguous	0.215	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/W	0.9628	likely_pathogenic	0.9327	pathogenic	-0.032	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
K/Y	0.8764	likely_pathogenic	0.8283	pathogenic	0.235	Stabilizing	1.0	D	0.827	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.