TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18457	55594;55595;55596	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
N2AB	16816	50671;50672;50673	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
N2A	15889	47890;47891;47892	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
N2B	9392	28399;28400;28401	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
Novex-1	9517	28774;28775;28776	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
Novex-2	9584	28975;28976;28977	chr2:178601721;178601720;178601719	chr2:179466448;179466447;179466446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-115
• Domain position: 76
• Structural Position: 154
• Q(SASA): 0.1194
• 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
Y/C	None	None	1.0	D	0.846	0.854	0.7991872175	gnomAD-4.0.0	2.74262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60081E-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
Y/A	0.9989	likely_pathogenic	0.9991	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/C	0.9875	likely_pathogenic	0.9906	pathogenic	-1.126	Destabilizing	1.0	D	0.846	deleterious	D	0.605597477	None	None	N
Y/D	0.9989	likely_pathogenic	0.9994	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.605597477	None	None	N
Y/E	0.9996	likely_pathogenic	0.9998	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/F	0.2474	likely_benign	0.2207	benign	-0.656	Destabilizing	0.999	D	0.7	prob.neutral	D	0.565999122	None	None	N
Y/G	0.9967	likely_pathogenic	0.9979	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/H	0.9922	likely_pathogenic	0.9945	pathogenic	-1.993	Destabilizing	1.0	D	0.787	deleterious	D	0.605395673	None	None	N
Y/I	0.9573	likely_pathogenic	0.9589	pathogenic	-0.607	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9997	pathogenic	-1.58	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/L	0.9281	likely_pathogenic	0.9253	pathogenic	-0.607	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
Y/M	0.9871	likely_pathogenic	0.9864	pathogenic	-0.615	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/N	0.9956	likely_pathogenic	0.9975	pathogenic	-2.521	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.605597477	None	None	N
Y/P	0.9994	likely_pathogenic	0.9997	pathogenic	-1.112	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
Y/Q	0.9996	likely_pathogenic	0.9997	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/R	0.9985	likely_pathogenic	0.999	pathogenic	-1.943	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/S	0.998	likely_pathogenic	0.9988	pathogenic	-2.748	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.605597477	None	None	N
Y/T	0.9989	likely_pathogenic	0.9993	pathogenic	-2.353	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/V	0.9633	likely_pathogenic	0.9681	pathogenic	-1.112	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/W	0.8356	likely_pathogenic	0.8339	pathogenic	-0.061	Destabilizing	1.0	D	0.779	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.