TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15837	47734;47735;47736	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
N2AB	14196	42811;42812;42813	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
N2A	13269	40030;40031;40032	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
N2B	6772	20539;20540;20541	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
Novex-1	6897	20914;20915;20916	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
Novex-2	6964	21115;21116;21117	chr2:178617842;178617841;178617840	chr2:179482569;179482568;179482567
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: Fn3-2
• Domain position: 80
• Structural Position: 112
• Q(SASA): 0.0883
• 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/Y	rs765708429	-0.834	0.999	D	0.798	0.652	0.764083912325	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
N/Y	rs765708429	-0.834	0.999	D	0.798	0.652	0.764083912325	gnomAD-4.0.0	1.59377E-06	None	None	None	None	N	None	0	0	None	0	2.78149E-05	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	0.9985	likely_pathogenic	0.9981	pathogenic	-0.633	Destabilizing	0.966	D	0.717	prob.delet.	None	None	None	None	N
N/C	0.9855	likely_pathogenic	0.9785	pathogenic	-0.657	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
N/D	0.9902	likely_pathogenic	0.9885	pathogenic	-2.381	Highly Destabilizing	0.977	D	0.629	neutral	D	0.674406928	None	None	N
N/E	0.9986	likely_pathogenic	0.9987	pathogenic	-2.202	Highly Destabilizing	0.983	D	0.704	prob.neutral	None	None	None	None	N
N/F	0.9997	likely_pathogenic	0.9995	pathogenic	-0.555	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
N/G	0.9929	likely_pathogenic	0.9916	pathogenic	-0.925	Destabilizing	0.983	D	0.601	neutral	None	None	None	None	N
N/H	0.9894	likely_pathogenic	0.9863	pathogenic	-0.681	Destabilizing	0.999	D	0.703	prob.neutral	D	0.755765191	None	None	N
N/I	0.997	likely_pathogenic	0.9964	pathogenic	0.105	Stabilizing	0.993	D	0.804	deleterious	D	0.789194252	None	None	N
N/K	0.9986	likely_pathogenic	0.9985	pathogenic	-0.26	Destabilizing	0.977	D	0.71	prob.delet.	D	0.754498774	None	None	N
N/L	0.9928	likely_pathogenic	0.9901	pathogenic	0.105	Stabilizing	0.99	D	0.779	deleterious	None	None	None	None	N
N/M	0.9966	likely_pathogenic	0.9953	pathogenic	0.165	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
N/P	0.9991	likely_pathogenic	0.999	pathogenic	-0.115	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
N/Q	0.9989	likely_pathogenic	0.9987	pathogenic	-1.086	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
N/R	0.9981	likely_pathogenic	0.9981	pathogenic	-0.289	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
N/S	0.9536	likely_pathogenic	0.9397	pathogenic	-1.051	Destabilizing	0.955	D	0.591	neutral	D	0.641217145	None	None	N
N/T	0.9805	likely_pathogenic	0.9713	pathogenic	-0.737	Destabilizing	0.362	N	0.379	neutral	D	0.585066271	None	None	N
N/V	0.9964	likely_pathogenic	0.9956	pathogenic	-0.115	Destabilizing	0.99	D	0.79	deleterious	None	None	None	None	N
N/W	0.9999	likely_pathogenic	0.9998	pathogenic	-0.669	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
N/Y	0.9956	likely_pathogenic	0.9947	pathogenic	-0.19	Destabilizing	0.999	D	0.798	deleterious	D	0.789108895	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.