TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24757	74494;74495;74496	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
N2AB	23116	69571;69572;69573	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
N2A	22189	66790;66791;66792	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
N2B	15692	47299;47300;47301	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
Novex-1	15817	47674;47675;47676	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
Novex-2	15884	47875;47876;47877	chr2:178571863;178571862;178571861	chr2:179436590;179436589;179436588
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-133
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.6809
• 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/R	None	None	0.001	N	0.28	0.107	0.199424873507	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

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	0.6749	likely_pathogenic	0.665	pathogenic	0.062	Stabilizing	0.157	N	0.519	neutral	None	None	None	None	N
K/C	0.7751	likely_pathogenic	0.7683	pathogenic	-0.341	Destabilizing	0.968	D	0.623	neutral	None	None	None	None	N
K/D	0.9182	likely_pathogenic	0.9208	pathogenic	-0.171	Destabilizing	0.567	D	0.451	neutral	None	None	None	None	N
K/E	0.5321	ambiguous	0.5286	ambiguous	-0.166	Destabilizing	0.124	N	0.529	neutral	D	0.528691087	None	None	N
K/F	0.8886	likely_pathogenic	0.8824	pathogenic	-0.216	Destabilizing	0.726	D	0.594	neutral	None	None	None	None	N
K/G	0.7648	likely_pathogenic	0.7587	pathogenic	-0.098	Destabilizing	0.272	N	0.462	neutral	None	None	None	None	N
K/H	0.4137	ambiguous	0.404	ambiguous	-0.247	Destabilizing	0.909	D	0.507	neutral	None	None	None	None	N
K/I	0.491	ambiguous	0.4758	ambiguous	0.404	Stabilizing	0.567	D	0.601	neutral	None	None	None	None	N
K/L	0.4935	ambiguous	0.4818	ambiguous	0.404	Stabilizing	0.157	N	0.481	neutral	None	None	None	None	N
K/M	0.4451	ambiguous	0.434	ambiguous	-0.025	Destabilizing	0.958	D	0.507	neutral	N	0.513119563	None	None	N
K/N	0.8046	likely_pathogenic	0.8075	pathogenic	0.081	Stabilizing	0.497	N	0.457	neutral	N	0.490060876	None	None	N
K/P	0.8183	likely_pathogenic	0.812	pathogenic	0.315	Stabilizing	0.726	D	0.496	neutral	None	None	None	None	N
K/Q	0.2069	likely_benign	0.1976	benign	-0.029	Destabilizing	0.497	N	0.49	neutral	N	0.487707473	None	None	N
K/R	0.0785	likely_benign	0.0766	benign	-0.073	Destabilizing	0.001	N	0.28	neutral	N	0.517108657	None	None	N
K/S	0.7677	likely_pathogenic	0.7665	pathogenic	-0.281	Destabilizing	0.157	N	0.5	neutral	None	None	None	None	N
K/T	0.4501	ambiguous	0.4413	ambiguous	-0.147	Destabilizing	0.002	N	0.311	neutral	N	0.519340885	None	None	N
K/V	0.4982	ambiguous	0.482	ambiguous	0.315	Stabilizing	0.396	N	0.442	neutral	None	None	None	None	N
K/W	0.8209	likely_pathogenic	0.816	pathogenic	-0.326	Destabilizing	0.968	D	0.654	neutral	None	None	None	None	N
K/Y	0.7775	likely_pathogenic	0.7704	pathogenic	0.034	Stabilizing	0.726	D	0.558	neutral	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.