TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29464	88615;88616;88617	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
N2AB	27823	83692;83693;83694	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
N2A	26896	80911;80912;80913	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
N2B	20399	61420;61421;61422	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
Novex-1	20524	61795;61796;61797	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
Novex-2	20591	61996;61997;61998	chr2:178555069;178555068;178555067	chr2:179419796;179419795;179419794
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-146
• Domain position: 21
• Structural Position: 35
• Q(SASA): 0.1859
• 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
I/L	rs1700847616	None	0.993	D	0.413	0.462	0.687289144923	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
I/L	rs1700847616	None	0.993	D	0.413	0.462	0.687289144923	gnomAD-4.0.0	6.57091E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.4162E-05	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
I/A	0.8874	likely_pathogenic	0.8888	pathogenic	-1.144	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
I/C	0.8709	likely_pathogenic	0.8774	pathogenic	-1.176	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
I/D	0.9938	likely_pathogenic	0.9937	pathogenic	0.291	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
I/E	0.9861	likely_pathogenic	0.986	pathogenic	0.308	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/F	0.2847	likely_benign	0.2846	benign	-0.697	Destabilizing	1.0	D	0.797	deleterious	N	0.470995152	None	None	N
I/G	0.976	likely_pathogenic	0.9755	pathogenic	-1.433	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
I/H	0.9488	likely_pathogenic	0.9488	pathogenic	-0.577	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/K	0.9385	likely_pathogenic	0.9337	pathogenic	-0.615	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/L	0.2695	likely_benign	0.2601	benign	-0.442	Destabilizing	0.993	D	0.413	neutral	D	0.523192054	None	None	N
I/M	0.2738	likely_benign	0.2739	benign	-0.638	Destabilizing	1.0	D	0.784	deleterious	N	0.505298884	None	None	N
I/N	0.905	likely_pathogenic	0.8972	pathogenic	-0.542	Destabilizing	1.0	D	0.861	deleterious	N	0.505805863	None	None	N
I/P	0.9856	likely_pathogenic	0.9874	pathogenic	-0.644	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/Q	0.9588	likely_pathogenic	0.958	pathogenic	-0.573	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/R	0.9148	likely_pathogenic	0.9112	pathogenic	-0.245	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/S	0.8958	likely_pathogenic	0.8934	pathogenic	-1.286	Destabilizing	1.0	D	0.817	deleterious	D	0.538142864	None	None	N
I/T	0.8547	likely_pathogenic	0.8498	pathogenic	-1.128	Destabilizing	1.0	D	0.774	deleterious	D	0.529291307	None	None	N
I/V	0.1334	likely_benign	0.1345	benign	-0.644	Destabilizing	0.993	D	0.368	neutral	N	0.404969656	None	None	N
I/W	0.9487	likely_pathogenic	0.9479	pathogenic	-0.687	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
I/Y	0.7596	likely_pathogenic	0.746	pathogenic	-0.47	Destabilizing	1.0	D	0.82	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.