TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14920	44983;44984;44985	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
N2AB	13279	40060;40061;40062	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
N2A	12352	37279;37280;37281	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
N2B	5855	17788;17789;17790	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
Novex-1	5980	18163;18164;18165	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
Novex-2	6047	18364;18365;18366	chr2:178624522;178624521;178624520	chr2:179489249;179489248;179489247
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-100
• Domain position: 68
• Structural Position: 152
• Q(SASA): 0.452
• 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
K/T	None	None	0.864	N	0.615	0.16	0.126345400529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
K/A	0.2598	likely_benign	0.348	ambiguous	-0.793	Destabilizing	0.707	D	0.588	neutral	None	None	None	None	N
K/C	0.6565	likely_pathogenic	0.7296	pathogenic	-0.681	Destabilizing	0.995	D	0.68	prob.neutral	None	None	None	None	N
K/D	0.5658	likely_pathogenic	0.6177	pathogenic	-0.569	Destabilizing	0.894	D	0.625	neutral	None	None	None	None	N
K/E	0.1809	likely_benign	0.1989	benign	-0.403	Destabilizing	0.477	N	0.556	neutral	N	0.336957644	None	None	N
K/F	0.8357	likely_pathogenic	0.8699	pathogenic	-0.209	Destabilizing	0.995	D	0.682	prob.neutral	None	None	None	None	N
K/G	0.2911	likely_benign	0.3673	ambiguous	-1.228	Destabilizing	0.894	D	0.623	neutral	None	None	None	None	N
K/H	0.3587	ambiguous	0.3785	ambiguous	-1.582	Destabilizing	0.985	D	0.652	neutral	None	None	None	None	N
K/I	0.5159	ambiguous	0.5905	pathogenic	0.375	Stabilizing	0.928	D	0.675	prob.neutral	N	0.338384681	None	None	N
K/L	0.455	ambiguous	0.4762	ambiguous	0.375	Stabilizing	0.894	D	0.623	neutral	None	None	None	None	N
K/M	0.2488	likely_benign	0.2859	benign	0.261	Stabilizing	0.995	D	0.647	neutral	None	None	None	None	N
K/N	0.4002	ambiguous	0.4614	ambiguous	-0.908	Destabilizing	0.864	D	0.608	neutral	N	0.336573463	None	None	N
K/P	0.8978	likely_pathogenic	0.9002	pathogenic	0.015	Stabilizing	0.945	D	0.645	neutral	None	None	None	None	N
K/Q	0.1172	likely_benign	0.1236	benign	-0.832	Destabilizing	0.864	D	0.605	neutral	N	0.337639146	None	None	N
K/R	0.0901	likely_benign	0.0829	benign	-0.985	Destabilizing	0.006	N	0.454	neutral	N	0.348007608	None	None	N
K/S	0.3481	ambiguous	0.4211	ambiguous	-1.504	Destabilizing	0.707	D	0.584	neutral	None	None	None	None	N
K/T	0.1879	likely_benign	0.2323	benign	-1.109	Destabilizing	0.864	D	0.615	neutral	N	0.348179834	None	None	N
K/V	0.4336	ambiguous	0.5093	ambiguous	0.015	Stabilizing	0.894	D	0.631	neutral	None	None	None	None	N
K/W	0.8521	likely_pathogenic	0.856	pathogenic	-0.142	Destabilizing	0.995	D	0.664	neutral	None	None	None	None	N
K/Y	0.6893	likely_pathogenic	0.7329	pathogenic	0.131	Stabilizing	0.981	D	0.662	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.