TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23473	70642;70643;70644	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
N2AB	21832	65719;65720;65721	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
N2A	20905	62938;62939;62940	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
N2B	14408	43447;43448;43449	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
Novex-1	14533	43822;43823;43824	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
Novex-2	14600	44023;44024;44025	chr2:178575715;178575714;178575713	chr2:179440442;179440441;179440440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-58
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1332
• 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
E/Q	None	None	1.0	N	0.764	0.316	0.27479166964	gnomAD-4.0.0	1.59176E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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
E/A	0.9193	likely_pathogenic	0.9275	pathogenic	-1.728	Destabilizing	1.0	D	0.691	prob.neutral	D	0.539799786	None	None	N
E/C	0.9928	likely_pathogenic	0.9941	pathogenic	-1.017	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/D	0.8815	likely_pathogenic	0.8783	pathogenic	-1.585	Destabilizing	0.998	D	0.664	neutral	N	0.47537171	None	None	N
E/F	0.9972	likely_pathogenic	0.9976	pathogenic	-1.445	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/G	0.9496	likely_pathogenic	0.9525	pathogenic	-2.121	Highly Destabilizing	1.0	D	0.747	deleterious	D	0.526432473	None	None	N
E/H	0.9893	likely_pathogenic	0.9887	pathogenic	-1.414	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.9866	likely_pathogenic	0.9884	pathogenic	-0.608	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/K	0.9657	likely_pathogenic	0.9692	pathogenic	-1.513	Destabilizing	1.0	D	0.686	prob.neutral	N	0.505286343	None	None	N
E/L	0.983	likely_pathogenic	0.9853	pathogenic	-0.608	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/M	0.9719	likely_pathogenic	0.9748	pathogenic	0.12	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/N	0.9822	likely_pathogenic	0.9817	pathogenic	-1.724	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/P	0.9999	likely_pathogenic	0.9999	pathogenic	-0.966	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.5578	ambiguous	0.5567	ambiguous	-1.509	Destabilizing	1.0	D	0.764	deleterious	N	0.521924539	None	None	N
E/R	0.9758	likely_pathogenic	0.9771	pathogenic	-1.283	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/S	0.9226	likely_pathogenic	0.9243	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/T	0.972	likely_pathogenic	0.9728	pathogenic	-2.046	Highly Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/V	0.9627	likely_pathogenic	0.9664	pathogenic	-0.966	Destabilizing	1.0	D	0.736	prob.delet.	N	0.519822654	None	None	N
E/W	0.9988	likely_pathogenic	0.999	pathogenic	-1.387	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
E/Y	0.9957	likely_pathogenic	0.996	pathogenic	-1.213	Destabilizing	1.0	D	0.782	deleterious	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.