TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9027	27304;27305;27306	chr2:178712946;178712945;178712944	chr2:179577673;179577672;179577671
N2AB	8710	26353;26354;26355	chr2:178712946;178712945;178712944	chr2:179577673;179577672;179577671
N2A	7783	23572;23573;23574	chr2:178712946;178712945;178712944	chr2:179577673;179577672;179577671
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-76
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.405
• 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
P/L	rs1356270449	None	None	N	0.276	0.204	0.386395597597	gnomAD-4.0.0	9.58509E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25977E-05	0	0
P/T	rs2154296309	None	0.012	N	0.339	0.032	0.0401082797425	gnomAD-4.0.0	1.36931E-06	None	None	None	None	N	None	0	0	None	0	5.04388E-05	None	0	0	0	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	0.062	likely_benign	0.0521	benign	-1.147	Destabilizing	None	N	0.109	neutral	N	0.486819382	None	None	N
P/C	0.4453	ambiguous	0.38	ambiguous	-0.462	Destabilizing	0.676	D	0.465	neutral	None	None	None	None	N
P/D	0.2612	likely_benign	0.247	benign	-1.0	Destabilizing	None	N	0.165	neutral	None	None	None	None	N
P/E	0.201	likely_benign	0.1843	benign	-1.042	Destabilizing	0.038	N	0.341	neutral	None	None	None	None	N
P/F	0.3637	ambiguous	0.3245	benign	-1.021	Destabilizing	0.12	N	0.512	neutral	None	None	None	None	N
P/G	0.2264	likely_benign	0.1992	benign	-1.407	Destabilizing	0.016	N	0.334	neutral	None	None	None	None	N
P/H	0.1524	likely_benign	0.1504	benign	-1.004	Destabilizing	0.295	N	0.447	neutral	N	0.457097693	None	None	N
P/I	0.2737	likely_benign	0.2356	benign	-0.551	Destabilizing	0.038	N	0.517	neutral	None	None	None	None	N
P/K	0.2122	likely_benign	0.2035	benign	-0.914	Destabilizing	0.038	N	0.352	neutral	None	None	None	None	N
P/L	0.1293	likely_benign	0.1207	benign	-0.551	Destabilizing	None	N	0.276	neutral	N	0.467947019	None	None	N
P/M	0.2713	likely_benign	0.2251	benign	-0.328	Destabilizing	0.214	N	0.46	neutral	None	None	None	None	N
P/N	0.2339	likely_benign	0.2085	benign	-0.528	Destabilizing	0.038	N	0.493	neutral	None	None	None	None	N
P/Q	0.1299	likely_benign	0.1238	benign	-0.737	Destabilizing	0.214	N	0.461	neutral	None	None	None	None	N
P/R	0.1363	likely_benign	0.1412	benign	-0.386	Destabilizing	0.171	N	0.519	neutral	N	0.479450693	None	None	N
P/S	0.085	likely_benign	0.0784	benign	-0.934	Destabilizing	None	N	0.106	neutral	N	0.416591293	None	None	N
P/T	0.0898	likely_benign	0.0806	benign	-0.876	Destabilizing	0.012	N	0.339	neutral	N	0.493398638	None	None	N
P/V	0.1892	likely_benign	0.1571	benign	-0.715	Destabilizing	0.038	N	0.398	neutral	None	None	None	None	N
P/W	0.5303	ambiguous	0.5283	ambiguous	-1.188	Destabilizing	0.864	D	0.541	neutral	None	None	None	None	N
P/Y	0.3381	likely_benign	0.3091	benign	-0.905	Destabilizing	0.356	N	0.509	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.