TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30227	90904;90905;90906	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
N2AB	28586	85981;85982;85983	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
N2A	27659	83200;83201;83202	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
N2B	21162	63709;63710;63711	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
Novex-1	21287	64084;64085;64086	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
Novex-2	21354	64285;64286;64287	chr2:178552221;178552220;178552219	chr2:179416948;179416947;179416946
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: Fn3-108
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3091
• 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/M	None	None	0.966	N	0.494	0.274	0.233785782151	gnomAD-4.0.0	2.05314E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79917E-06	0	1.65722E-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	0.1999	likely_benign	0.2067	benign	-0.473	Destabilizing	0.688	D	0.402	neutral	None	None	None	None	N
K/C	0.5115	ambiguous	0.5705	pathogenic	-0.533	Destabilizing	0.998	D	0.498	neutral	None	None	None	None	N
K/D	0.6229	likely_pathogenic	0.6173	pathogenic	-0.104	Destabilizing	0.842	D	0.493	neutral	None	None	None	None	N
K/E	0.1632	likely_benign	0.1592	benign	None	Stabilizing	0.454	N	0.355	neutral	N	0.461787652	None	None	N
K/F	0.6546	likely_pathogenic	0.7001	pathogenic	-0.1	Destabilizing	0.974	D	0.535	neutral	None	None	None	None	N
K/G	0.4646	ambiguous	0.4892	ambiguous	-0.839	Destabilizing	0.915	D	0.482	neutral	None	None	None	None	N
K/H	0.3544	ambiguous	0.3701	ambiguous	-1.171	Destabilizing	0.974	D	0.495	neutral	None	None	None	None	N
K/I	0.1717	likely_benign	0.1897	benign	0.471	Stabilizing	0.067	N	0.275	neutral	None	None	None	None	N
K/L	0.2363	likely_benign	0.2564	benign	0.471	Stabilizing	0.525	D	0.392	neutral	None	None	None	None	N
K/M	0.1743	likely_benign	0.1734	benign	0.278	Stabilizing	0.966	D	0.494	neutral	N	0.452706809	None	None	N
K/N	0.4346	ambiguous	0.4209	ambiguous	-0.448	Destabilizing	0.801	D	0.382	neutral	N	0.496246942	None	None	N
K/P	0.2628	likely_benign	0.2904	benign	0.187	Stabilizing	0.991	D	0.509	neutral	None	None	None	None	N
K/Q	0.1165	likely_benign	0.1193	benign	-0.51	Destabilizing	0.136	N	0.181	neutral	N	0.47129257	None	None	N
K/R	0.0853	likely_benign	0.092	benign	-0.68	Destabilizing	0.012	N	0.165	neutral	N	0.471119211	None	None	N
K/S	0.3248	likely_benign	0.3302	benign	-1.069	Destabilizing	0.842	D	0.319	neutral	None	None	None	None	N
K/T	0.1442	likely_benign	0.143	benign	-0.762	Destabilizing	0.801	D	0.444	neutral	N	0.465924035	None	None	N
K/V	0.1535	likely_benign	0.1742	benign	0.187	Stabilizing	0.029	N	0.153	neutral	None	None	None	None	N
K/W	0.8036	likely_pathogenic	0.8475	pathogenic	0.014	Stabilizing	0.998	D	0.545	neutral	None	None	None	None	N
K/Y	0.5618	ambiguous	0.5909	pathogenic	0.285	Stabilizing	0.991	D	0.524	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.