TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19433	58522;58523;58524	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
N2AB	17792	53599;53600;53601	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
N2A	16865	50818;50819;50820	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
N2B	10368	31327;31328;31329	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
Novex-1	10493	31702;31703;31704	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
Novex-2	10560	31903;31904;31905	chr2:178594096;178594095;178594094	chr2:179458823;179458822;179458821
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: Ig-118
• Domain position: 43
• Structural Position: 121
• Q(SASA): 0.2189
• 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/A	None	None	0.78	N	0.554	0.139	0.338834610459	gnomAD-4.0.0	2.05301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69869E-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
T/A	0.1348	likely_benign	0.1383	benign	-0.699	Destabilizing	0.78	D	0.554	neutral	N	0.486977751	None	None	N
T/C	0.3045	likely_benign	0.3317	benign	-0.648	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.5834	likely_pathogenic	0.5346	ambiguous	-1.813	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
T/E	0.5675	likely_pathogenic	0.5122	ambiguous	-1.686	Destabilizing	0.996	D	0.68	prob.neutral	None	None	None	None	N
T/F	0.3162	likely_benign	0.3239	benign	-0.395	Destabilizing	0.976	D	0.703	prob.neutral	None	None	None	None	N
T/G	0.3661	ambiguous	0.3638	ambiguous	-1.066	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
T/H	0.4255	ambiguous	0.4071	ambiguous	-1.447	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
T/I	0.1466	likely_benign	0.1506	benign	0.233	Stabilizing	0.011	N	0.338	neutral	N	0.404340512	None	None	N
T/K	0.5489	ambiguous	0.4756	ambiguous	-0.909	Destabilizing	0.988	D	0.681	prob.neutral	None	None	None	None	N
T/L	0.1239	likely_benign	0.1248	benign	0.233	Stabilizing	0.702	D	0.514	neutral	None	None	None	None	N
T/M	0.1177	likely_benign	0.1189	benign	0.384	Stabilizing	0.976	D	0.704	prob.neutral	None	None	None	None	N
T/N	0.1949	likely_benign	0.1874	benign	-1.45	Destabilizing	0.995	D	0.616	neutral	N	0.487365078	None	None	N
T/P	0.6964	likely_pathogenic	0.6583	pathogenic	-0.045	Destabilizing	0.995	D	0.706	prob.neutral	N	0.487365078	None	None	N
T/Q	0.4623	ambiguous	0.4249	ambiguous	-1.333	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	N
T/R	0.4545	ambiguous	0.3908	ambiguous	-0.984	Destabilizing	0.996	D	0.713	prob.delet.	None	None	None	None	N
T/S	0.1557	likely_benign	0.1594	benign	-1.461	Destabilizing	0.946	D	0.558	neutral	N	0.513894993	None	None	N
T/V	0.1421	likely_benign	0.1498	benign	-0.045	Destabilizing	0.507	D	0.437	neutral	None	None	None	None	N
T/W	0.6486	likely_pathogenic	0.6248	pathogenic	-0.661	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.3464	ambiguous	0.3421	ambiguous	-0.296	Destabilizing	0.996	D	0.727	prob.delet.	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.