TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17032	51319;51320;51321	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
N2AB	15391	46396;46397;46398	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
N2A	14464	43615;43616;43617	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
N2B	7967	24124;24125;24126	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
Novex-1	8092	24499;24500;24501	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
Novex-2	8159	24700;24701;24702	chr2:178611035;178611034;178611033	chr2:179475762;179475761;179475760
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-111
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.818
• Predicted PPI site: I

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	rs777424760	0.224	0.001	N	0.249	0.172	0.146414634003	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/N	rs777424760	0.224	0.001	N	0.249	0.172	0.146414634003	gnomAD-4.0.0	3.18746E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72607E-06	0	0
K/R	None	None	None	N	0.265	0.098	0.148003135375	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-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	0.2295	likely_benign	0.244	benign	0.024	Stabilizing	0.002	N	0.215	neutral	None	None	None	None	I
K/C	0.6494	likely_pathogenic	0.647	pathogenic	-0.389	Destabilizing	0.935	D	0.326	neutral	None	None	None	None	I
K/D	0.3934	ambiguous	0.3903	ambiguous	-0.154	Destabilizing	0.081	N	0.395	neutral	None	None	None	None	I
K/E	0.1596	likely_benign	0.1666	benign	-0.154	Destabilizing	0.062	N	0.33	neutral	N	0.450923787	None	None	I
K/F	0.7412	likely_pathogenic	0.7518	pathogenic	-0.275	Destabilizing	0.791	D	0.33	neutral	None	None	None	None	I
K/G	0.3167	likely_benign	0.3221	benign	-0.132	Destabilizing	0.081	N	0.365	neutral	None	None	None	None	I
K/H	0.2572	likely_benign	0.2637	benign	-0.293	Destabilizing	0.38	N	0.351	neutral	None	None	None	None	I
K/I	0.2601	likely_benign	0.2882	benign	0.355	Stabilizing	0.555	D	0.357	neutral	None	None	None	None	I
K/L	0.3149	likely_benign	0.3188	benign	0.355	Stabilizing	0.149	N	0.383	neutral	None	None	None	None	I
K/M	0.2128	likely_benign	0.2203	benign	-0.008	Destabilizing	0.915	D	0.351	neutral	N	0.51573258	None	None	I
K/N	0.2799	likely_benign	0.2968	benign	0.042	Stabilizing	0.001	N	0.249	neutral	N	0.513807335	None	None	I
K/P	0.3661	ambiguous	0.3479	ambiguous	0.27	Stabilizing	0.001	N	0.242	neutral	None	None	None	None	I
K/Q	0.1251	likely_benign	0.1332	benign	-0.083	Destabilizing	0.317	N	0.309	neutral	N	0.513305208	None	None	I
K/R	0.0886	likely_benign	0.0867	benign	-0.091	Destabilizing	None	N	0.265	neutral	N	0.496809114	None	None	I
K/S	0.2469	likely_benign	0.2648	benign	-0.349	Destabilizing	0.007	N	0.285	neutral	None	None	None	None	I
K/T	0.1137	likely_benign	0.1273	benign	-0.216	Destabilizing	0.062	N	0.385	neutral	N	0.504476498	None	None	I
K/V	0.2419	likely_benign	0.2613	benign	0.27	Stabilizing	0.149	N	0.363	neutral	None	None	None	None	I
K/W	0.8011	likely_pathogenic	0.7863	pathogenic	-0.367	Destabilizing	0.935	D	0.437	neutral	None	None	None	None	I
K/Y	0.5927	likely_pathogenic	0.5932	pathogenic	-0.005	Destabilizing	0.791	D	0.361	neutral	None	None	None	None	I

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.