TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29821	89686;89687;89688	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
N2AB	28180	84763;84764;84765	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
N2A	27253	81982;81983;81984	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
N2B	20756	62491;62492;62493	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
Novex-1	20881	62866;62867;62868	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
Novex-2	20948	63067;63068;63069	chr2:178553544;178553543;178553542	chr2:179418271;179418270;179418269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-105
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.2791
• 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
P/A	rs1469989307	None	0.134	N	0.283	0.193	0.149567049428	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	2.88018E-04	0	None	0	0	0	0	0
P/A	rs1469989307	None	0.134	N	0.283	0.193	0.149567049428	gnomAD-4.0.0	6.57177E-06	None	None	None	None	I	None	0	0	None	2.88018E-04	0	None	0	0	0	0	0
P/S	None	None	0.31	N	0.299	0.261	0.16115917748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
P/A	0.0932	likely_benign	0.0894	benign	-1.669	Destabilizing	0.134	N	0.283	neutral	N	0.463745008	None	None	I
P/C	0.5273	ambiguous	0.5219	ambiguous	-1.11	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	I
P/D	0.6427	likely_pathogenic	0.6027	pathogenic	-1.733	Destabilizing	0.02	N	0.289	neutral	None	None	None	None	I
P/E	0.5763	likely_pathogenic	0.541	ambiguous	-1.75	Destabilizing	0.884	D	0.495	neutral	None	None	None	None	I
P/F	0.5665	likely_pathogenic	0.5376	ambiguous	-1.338	Destabilizing	0.997	D	0.657	neutral	None	None	None	None	I
P/G	0.3869	ambiguous	0.3881	ambiguous	-1.963	Destabilizing	0.863	D	0.52	neutral	None	None	None	None	I
P/H	0.3055	likely_benign	0.2829	benign	-1.41	Destabilizing	0.999	D	0.62	neutral	N	0.494917543	None	None	I
P/I	0.5774	likely_pathogenic	0.5292	ambiguous	-0.956	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	I
P/K	0.5539	ambiguous	0.5325	ambiguous	-1.357	Destabilizing	0.939	D	0.481	neutral	None	None	None	None	I
P/L	0.3544	ambiguous	0.32	benign	-0.956	Destabilizing	0.92	D	0.589	neutral	N	0.492636137	None	None	I
P/M	0.5256	ambiguous	0.4908	ambiguous	-0.725	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
P/N	0.5197	ambiguous	0.4902	ambiguous	-1.131	Destabilizing	0.939	D	0.561	neutral	None	None	None	None	I
P/Q	0.3755	ambiguous	0.3551	ambiguous	-1.375	Destabilizing	0.991	D	0.533	neutral	None	None	None	None	I
P/R	0.4252	ambiguous	0.4037	ambiguous	-0.739	Destabilizing	0.988	D	0.602	neutral	N	0.50525989	None	None	I
P/S	0.1879	likely_benign	0.1793	benign	-1.609	Destabilizing	0.31	N	0.299	neutral	N	0.481622227	None	None	I
P/T	0.2158	likely_benign	0.2004	benign	-1.531	Destabilizing	0.852	D	0.505	neutral	N	0.485763283	None	None	I
P/V	0.3894	ambiguous	0.3599	ambiguous	-1.161	Destabilizing	0.939	D	0.545	neutral	None	None	None	None	I
P/W	0.7363	likely_pathogenic	0.7035	pathogenic	-1.474	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
P/Y	0.5276	ambiguous	0.5009	ambiguous	-1.228	Destabilizing	0.997	D	0.662	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.