TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24275	73048;73049;73050	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
N2AB	22634	68125;68126;68127	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
N2A	21707	65344;65345;65346	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
N2B	15210	45853;45854;45855	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
Novex-1	15335	46228;46229;46230	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
Novex-2	15402	46429;46430;46431	chr2:178573309;178573308;178573307	chr2:179438036;179438035;179438034
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-64
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.4478
• 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/I	rs199860952	0.616	0.317	N	0.334	0.135	None	gnomAD-2.1.1	4.57E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	1.00644E-04	7.83E-05	0
K/I	rs199860952	0.616	0.317	N	0.334	0.135	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	I	None	0	0	0	0	0	None	9.42E-05	0	1.32376E-04	0	0
K/I	rs199860952	0.616	0.317	N	0.334	0.135	None	gnomAD-4.0.0	1.2624E-04	None	None	None	None	I	None	0	0	None	0	0	None	6.35789E-05	0	1.64446E-04	0	6.58393E-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	0.5049	ambiguous	0.479	ambiguous	0.071	Stabilizing	0.035	N	0.287	neutral	None	None	None	None	I
K/C	0.7038	likely_pathogenic	0.7197	pathogenic	-0.316	Destabilizing	0.935	D	0.232	neutral	None	None	None	None	I
K/D	0.6947	likely_pathogenic	0.6675	pathogenic	-0.198	Destabilizing	0.149	N	0.362	neutral	None	None	None	None	I
K/E	0.3834	ambiguous	0.3424	ambiguous	-0.205	Destabilizing	0.027	N	0.264	neutral	N	0.475786817	None	None	I
K/F	0.8477	likely_pathogenic	0.8396	pathogenic	-0.251	Destabilizing	0.555	D	0.263	neutral	None	None	None	None	I
K/G	0.5362	ambiguous	0.5194	ambiguous	-0.067	Destabilizing	0.149	N	0.315	neutral	None	None	None	None	I
K/H	0.3225	likely_benign	0.3231	benign	-0.199	Destabilizing	0.555	D	0.233	neutral	None	None	None	None	I
K/I	0.5328	ambiguous	0.5272	ambiguous	0.355	Stabilizing	0.317	N	0.334	neutral	N	0.488025396	None	None	I
K/L	0.5305	ambiguous	0.5207	ambiguous	0.355	Stabilizing	0.081	N	0.311	neutral	None	None	None	None	I
K/M	0.3883	ambiguous	0.3821	ambiguous	-0.038	Destabilizing	0.791	D	0.231	neutral	None	None	None	None	I
K/N	0.5238	ambiguous	0.4916	ambiguous	0.148	Stabilizing	0.117	N	0.229	neutral	N	0.449891082	None	None	I
K/P	0.8807	likely_pathogenic	0.8833	pathogenic	0.284	Stabilizing	0.555	D	0.341	neutral	None	None	None	None	I
K/Q	0.1827	likely_benign	0.1717	benign	0.018	Stabilizing	0.117	N	0.251	neutral	N	0.465148536	None	None	I
K/R	0.0734	likely_benign	0.0718	benign	-0.033	Destabilizing	None	N	0.103	neutral	N	0.429419809	None	None	I
K/S	0.5867	likely_pathogenic	0.5607	ambiguous	-0.21	Destabilizing	0.035	N	0.223	neutral	None	None	None	None	I
K/T	0.2921	likely_benign	0.2873	benign	-0.096	Destabilizing	None	N	0.148	neutral	N	0.4280143	None	None	I
K/V	0.4778	ambiguous	0.4731	ambiguous	0.284	Stabilizing	0.081	N	0.333	neutral	None	None	None	None	I
K/W	0.7689	likely_pathogenic	0.7681	pathogenic	-0.365	Destabilizing	0.935	D	0.251	neutral	None	None	None	None	I
K/Y	0.6788	likely_pathogenic	0.668	pathogenic	-0.006	Destabilizing	0.555	D	0.267	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.