TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14124	42595;42596;42597	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
N2AB	12483	37672;37673;37674	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
N2A	11556	34891;34892;34893	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
N2B	5059	15400;15401;15402	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
Novex-1	5184	15775;15776;15777	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
Novex-2	5251	15976;15977;15978	chr2:178634411;178634410;178634409	chr2:179499138;179499137;179499136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-91
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0729
• 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
A/S	rs753046446	-1.332	0.959	N	0.678	0.297	0.216624796971	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
A/S	rs753046446	-1.332	0.959	N	0.678	0.297	0.216624796971	gnomAD-4.0.0	3.19122E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72426E-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
A/C	0.6853	likely_pathogenic	0.6033	pathogenic	-0.909	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
A/D	0.9973	likely_pathogenic	0.9939	pathogenic	-1.967	Destabilizing	0.996	D	0.856	deleterious	N	0.465225829	None	None	N
A/E	0.9919	likely_pathogenic	0.9835	pathogenic	-1.728	Destabilizing	0.997	D	0.792	deleterious	None	None	None	None	N
A/F	0.9677	likely_pathogenic	0.9452	pathogenic	-0.424	Destabilizing	0.991	D	0.856	deleterious	None	None	None	None	N
A/G	0.4948	ambiguous	0.4694	ambiguous	-1.337	Destabilizing	0.986	D	0.688	prob.neutral	N	0.465225829	None	None	N
A/H	0.9972	likely_pathogenic	0.9934	pathogenic	-1.887	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
A/I	0.7393	likely_pathogenic	0.6537	pathogenic	0.636	Stabilizing	0.079	N	0.573	neutral	None	None	None	None	N
A/K	0.9982	likely_pathogenic	0.9962	pathogenic	-0.749	Destabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
A/L	0.6365	likely_pathogenic	0.5843	pathogenic	0.636	Stabilizing	0.759	D	0.616	neutral	None	None	None	None	N
A/M	0.788	likely_pathogenic	0.699	pathogenic	0.228	Stabilizing	0.991	D	0.803	deleterious	None	None	None	None	N
A/N	0.9902	likely_pathogenic	0.9784	pathogenic	-1.145	Destabilizing	0.997	D	0.867	deleterious	None	None	None	None	N
A/P	0.9939	likely_pathogenic	0.9922	pathogenic	0.2	Stabilizing	0.996	D	0.804	deleterious	N	0.465225829	None	None	N
A/Q	0.9863	likely_pathogenic	0.9772	pathogenic	-0.857	Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
A/R	0.9926	likely_pathogenic	0.9884	pathogenic	-1.075	Destabilizing	0.997	D	0.804	deleterious	None	None	None	None	N
A/S	0.5253	ambiguous	0.4084	ambiguous	-1.595	Destabilizing	0.959	D	0.678	prob.neutral	N	0.465225829	None	None	N
A/T	0.5248	ambiguous	0.3704	ambiguous	-1.208	Destabilizing	0.92	D	0.687	prob.neutral	N	0.463906865	None	None	N
A/V	0.3929	ambiguous	0.3232	benign	0.2	Stabilizing	0.134	N	0.45	neutral	N	0.402051211	None	None	N
A/W	0.9984	likely_pathogenic	0.9969	pathogenic	-1.25	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
A/Y	0.993	likely_pathogenic	0.9848	pathogenic	-0.624	Destabilizing	0.997	D	0.867	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.