TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32550	97873;97874;97875	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
N2AB	30909	92950;92951;92952	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
N2A	29982	90169;90170;90171	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
N2B	23485	70678;70679;70680	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
Novex-1	23610	71053;71054;71055	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
Novex-2	23677	71254;71255;71256	chr2:178541429;178541428;178541427	chr2:179406156;179406155;179406154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-125
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1048
• 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
N/T	None	None	0.996	N	0.594	0.375	0.290590437066	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-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
N/A	0.7459	likely_pathogenic	0.7619	pathogenic	-0.923	Destabilizing	0.994	D	0.56	neutral	None	None	None	None	N
N/C	0.4939	ambiguous	0.4569	ambiguous	-0.101	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
N/D	0.7516	likely_pathogenic	0.7858	pathogenic	-0.908	Destabilizing	0.996	D	0.566	neutral	N	0.472560553	None	None	N
N/E	0.9621	likely_pathogenic	0.9665	pathogenic	-0.694	Destabilizing	0.997	D	0.616	neutral	None	None	None	None	N
N/F	0.9848	likely_pathogenic	0.986	pathogenic	-0.457	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
N/G	0.6181	likely_pathogenic	0.6232	pathogenic	-1.34	Destabilizing	0.997	D	0.542	neutral	None	None	None	None	N
N/H	0.6902	likely_pathogenic	0.6941	pathogenic	-0.832	Destabilizing	1.0	D	0.723	prob.delet.	N	0.477284268	None	None	N
N/I	0.8655	likely_pathogenic	0.8837	pathogenic	0.184	Stabilizing	0.999	D	0.726	prob.delet.	N	0.48186617	None	None	N
N/K	0.9827	likely_pathogenic	0.9858	pathogenic	-0.07	Destabilizing	0.996	D	0.618	neutral	N	0.476586251	None	None	N
N/L	0.8313	likely_pathogenic	0.8488	pathogenic	0.184	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
N/M	0.8618	likely_pathogenic	0.8741	pathogenic	0.387	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
N/P	0.9547	likely_pathogenic	0.9588	pathogenic	-0.156	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
N/Q	0.9322	likely_pathogenic	0.9416	pathogenic	-0.614	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/R	0.9755	likely_pathogenic	0.9796	pathogenic	-0.3	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
N/S	0.1022	likely_benign	0.1076	benign	-1.02	Destabilizing	0.905	D	0.395	neutral	N	0.515843928	None	None	N
N/T	0.2686	likely_benign	0.2733	benign	-0.593	Destabilizing	0.996	D	0.594	neutral	N	0.513168983	None	None	N
N/V	0.8057	likely_pathogenic	0.815	pathogenic	-0.156	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
N/W	0.9918	likely_pathogenic	0.9927	pathogenic	-0.261	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
N/Y	0.9093	likely_pathogenic	0.9189	pathogenic	0.053	Stabilizing	1.0	D	0.711	prob.delet.	N	0.481665587	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.