TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28500	85723;85724;85725	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
N2AB	26859	80800;80801;80802	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
N2A	25932	78019;78020;78021	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
N2B	19435	58528;58529;58530	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
Novex-1	19560	58903;58904;58905	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
Novex-2	19627	59104;59105;59106	chr2:178560634;178560633;178560632	chr2:179425361;179425360;179425359
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-95
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.6617
• 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
I/V	rs752991005	-0.244	0.08	N	0.239	0.061	0.536988229258	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs752991005	-0.244	0.08	N	0.239	0.061	0.536988229258	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs752991005	-0.244	0.08	N	0.239	0.061	0.536988229258	gnomAD-4.0.0	6.57151E-06	None	None	None	None	I	None	2.41255E-05	0	None	0	0	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
I/A	0.2234	likely_benign	0.2631	benign	-1.024	Destabilizing	0.345	N	0.429	neutral	None	None	None	None	I
I/C	0.5202	ambiguous	0.601	pathogenic	-0.663	Destabilizing	0.991	D	0.47	neutral	None	None	None	None	I
I/D	0.5694	likely_pathogenic	0.6461	pathogenic	-0.521	Destabilizing	0.901	D	0.489	neutral	None	None	None	None	I
I/E	0.4457	ambiguous	0.5086	ambiguous	-0.597	Destabilizing	0.561	D	0.501	neutral	None	None	None	None	I
I/F	0.144	likely_benign	0.1567	benign	-0.867	Destabilizing	0.818	D	0.427	neutral	None	None	None	None	I
I/G	0.4923	ambiguous	0.5722	pathogenic	-1.242	Destabilizing	0.561	D	0.505	neutral	None	None	None	None	I
I/H	0.3601	ambiguous	0.4227	ambiguous	-0.462	Destabilizing	0.991	D	0.461	neutral	None	None	None	None	I
I/K	0.2551	likely_benign	0.2912	benign	-0.638	Destabilizing	0.326	N	0.473	neutral	N	0.442076888	None	None	I
I/L	0.0834	likely_benign	0.0871	benign	-0.548	Destabilizing	None	N	0.143	neutral	N	0.418605383	None	None	I
I/M	0.103	likely_benign	0.1109	benign	-0.412	Destabilizing	0.772	D	0.459	neutral	N	0.494025861	None	None	I
I/N	0.196	likely_benign	0.2343	benign	-0.383	Destabilizing	0.901	D	0.501	neutral	None	None	None	None	I
I/P	0.4197	ambiguous	0.5243	ambiguous	-0.673	Destabilizing	0.004	N	0.341	neutral	None	None	None	None	I
I/Q	0.3034	likely_benign	0.3614	ambiguous	-0.642	Destabilizing	0.818	D	0.503	neutral	None	None	None	None	I
I/R	0.1806	likely_benign	0.2055	benign	0.004	Stabilizing	0.003	N	0.378	neutral	N	0.461932086	None	None	I
I/S	0.2098	likely_benign	0.2583	benign	-0.889	Destabilizing	0.561	D	0.443	neutral	None	None	None	None	I
I/T	0.1823	likely_benign	0.2197	benign	-0.858	Destabilizing	0.491	N	0.42	neutral	N	0.396861887	None	None	I
I/V	0.0629	likely_benign	0.0653	benign	-0.673	Destabilizing	0.08	N	0.239	neutral	N	0.396112525	None	None	I
I/W	0.6969	likely_pathogenic	0.7322	pathogenic	-0.87	Destabilizing	0.991	D	0.497	neutral	None	None	None	None	I
I/Y	0.3959	ambiguous	0.4379	ambiguous	-0.645	Destabilizing	0.901	D	0.483	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.