TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28696	86311;86312;86313	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
N2AB	27055	81388;81389;81390	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
N2A	26128	78607;78608;78609	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
N2B	19631	59116;59117;59118	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
Novex-1	19756	59491;59492;59493	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
Novex-2	19823	59692;59693;59694	chr2:178560046;178560045;178560044	chr2:179424773;179424772;179424771
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-97
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8365
• 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
T/I	None	None	0.939	N	0.439	0.202	0.323342291347	gnomAD-4.0.0	6.84249E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	0
T/N	None	None	0.684	N	0.323	0.208	0.236890367714	gnomAD-4.0.0	6.84249E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	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
T/A	0.0678	likely_benign	0.0683	benign	-0.173	Destabilizing	0.309	N	0.366	neutral	N	0.458990568	None	None	N
T/C	0.2984	likely_benign	0.2883	benign	-0.25	Destabilizing	0.996	D	0.444	neutral	None	None	None	None	N
T/D	0.2025	likely_benign	0.1858	benign	0.001	Stabilizing	0.004	N	0.185	neutral	None	None	None	None	N
T/E	0.1774	likely_benign	0.1643	benign	-0.091	Destabilizing	0.373	N	0.405	neutral	None	None	None	None	N
T/F	0.2122	likely_benign	0.2047	benign	-0.826	Destabilizing	0.984	D	0.417	neutral	None	None	None	None	N
T/G	0.1518	likely_benign	0.1458	benign	-0.237	Destabilizing	0.373	N	0.376	neutral	None	None	None	None	N
T/H	0.2137	likely_benign	0.2155	benign	-0.385	Destabilizing	0.984	D	0.43	neutral	None	None	None	None	N
T/I	0.1142	likely_benign	0.1118	benign	-0.125	Destabilizing	0.939	D	0.439	neutral	N	0.480963351	None	None	N
T/K	0.142	likely_benign	0.1498	benign	-0.238	Destabilizing	0.742	D	0.39	neutral	None	None	None	None	N
T/L	0.0858	likely_benign	0.082	benign	-0.125	Destabilizing	0.742	D	0.389	neutral	None	None	None	None	N
T/M	0.083	likely_benign	0.0832	benign	-0.125	Destabilizing	0.996	D	0.431	neutral	None	None	None	None	N
T/N	0.0893	likely_benign	0.0878	benign	0.038	Stabilizing	0.684	D	0.323	neutral	N	0.433900122	None	None	N
T/P	0.0894	likely_benign	0.0846	benign	-0.117	Destabilizing	0.007	N	0.28	neutral	N	0.454064751	None	None	N
T/Q	0.1778	likely_benign	0.1825	benign	-0.189	Destabilizing	0.953	D	0.44	neutral	None	None	None	None	N
T/R	0.141	likely_benign	0.1464	benign	0.073	Stabilizing	0.91	D	0.44	neutral	None	None	None	None	N
T/S	0.0827	likely_benign	0.0816	benign	-0.133	Destabilizing	0.012	N	0.135	neutral	N	0.407831029	None	None	N
T/V	0.0984	likely_benign	0.0956	benign	-0.117	Destabilizing	0.742	D	0.323	neutral	None	None	None	None	N
T/W	0.5202	ambiguous	0.5071	ambiguous	-0.909	Destabilizing	0.996	D	0.462	neutral	None	None	None	None	N
T/Y	0.2482	likely_benign	0.2405	benign	-0.588	Destabilizing	0.984	D	0.422	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.