TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18419	55480;55481;55482	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
N2AB	16778	50557;50558;50559	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
N2A	15851	47776;47777;47778	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
N2B	9354	28285;28286;28287	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
Novex-1	9479	28660;28661;28662	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
Novex-2	9546	28861;28862;28863	chr2:178602016;178602015;178602014	chr2:179466743;179466742;179466741
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: Ig-115
• Domain position: 38
• Structural Position: 58
• Q(SASA): 0.1566
• 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	rs756145817	-0.266	0.034	N	0.381	0.129	0.282179105231	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs756145817	-0.266	0.034	N	0.381	0.129	0.282179105231	gnomAD-4.0.0	3.18656E-06	None	None	None	None	N	None	5.67086E-05	0	None	0	0	None	0	0	0	1.43373E-05	0
K/Q	None	None	0.901	N	0.566	0.188	0.221734844693	gnomAD-4.0.0	1.59328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43373E-05	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	0.2578	likely_benign	0.229	benign	0.075	Stabilizing	0.633	D	0.55	neutral	None	None	None	None	N
K/C	0.6727	likely_pathogenic	0.6296	pathogenic	-0.297	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
K/D	0.49	ambiguous	0.4367	ambiguous	-0.156	Destabilizing	0.633	D	0.606	neutral	None	None	None	None	N
K/E	0.1625	likely_benign	0.1442	benign	-0.165	Destabilizing	0.034	N	0.381	neutral	N	0.467661271	None	None	N
K/F	0.7615	likely_pathogenic	0.7222	pathogenic	-0.211	Destabilizing	0.961	D	0.779	deleterious	None	None	None	None	N
K/G	0.3138	likely_benign	0.2864	benign	-0.076	Destabilizing	0.775	D	0.645	neutral	None	None	None	None	N
K/H	0.3991	ambiguous	0.3519	ambiguous	-0.208	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
K/I	0.3574	ambiguous	0.3125	benign	0.389	Stabilizing	0.858	D	0.767	deleterious	None	None	None	None	N
K/L	0.3285	likely_benign	0.2897	benign	0.389	Stabilizing	0.633	D	0.643	neutral	None	None	None	None	N
K/M	0.2793	likely_benign	0.2504	benign	0.046	Stabilizing	0.986	D	0.655	neutral	N	0.485649599	None	None	N
K/N	0.3994	ambiguous	0.3413	ambiguous	0.182	Stabilizing	0.901	D	0.555	neutral	N	0.486516391	None	None	N
K/P	0.3483	ambiguous	0.3238	benign	0.309	Stabilizing	0.961	D	0.658	neutral	None	None	None	None	N
K/Q	0.1341	likely_benign	0.1223	benign	0.02	Stabilizing	0.901	D	0.566	neutral	N	0.452846535	None	None	N
K/R	0.0853	likely_benign	0.0841	benign	-0.011	Destabilizing	0.722	D	0.601	neutral	N	0.505198152	None	None	N
K/S	0.3421	ambiguous	0.2915	benign	-0.215	Destabilizing	0.633	D	0.554	neutral	None	None	None	None	N
K/T	0.188	likely_benign	0.161	benign	-0.1	Destabilizing	0.008	N	0.398	neutral	N	0.503117852	None	None	N
K/V	0.2842	likely_benign	0.2495	benign	0.309	Stabilizing	0.858	D	0.649	neutral	None	None	None	None	N
K/W	0.7752	likely_pathogenic	0.7554	pathogenic	-0.29	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
K/Y	0.6935	likely_pathogenic	0.6566	pathogenic	0.066	Stabilizing	0.987	D	0.725	prob.delet.	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.