TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33691	101296;101297;101298	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
N2AB	32050	96373;96374;96375	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
N2A	31123	93592;93593;93594	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
N2B	24626	74101;74102;74103	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
Novex-1	24751	74476;74477;74478	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
Novex-2	24818	74677;74678;74679	chr2:178535544;178535543;178535542	chr2:179400271;179400270;179400269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-132
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.3639
• 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
D/E	rs1342398434	-0.733	0.12	N	0.485	0.114	0.190952846119	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
D/E	rs1342398434	-0.733	0.12	N	0.485	0.114	0.190952846119	gnomAD-4.0.0	3.18235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71595E-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
D/A	0.4248	ambiguous	0.3018	benign	-0.409	Destabilizing	0.997	D	0.853	deleterious	N	0.476154951	None	None	N
D/C	0.8967	likely_pathogenic	0.8435	pathogenic	-0.121	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
D/E	0.3628	ambiguous	0.303	benign	-0.826	Destabilizing	0.12	N	0.485	neutral	N	0.507091159	None	None	N
D/F	0.8761	likely_pathogenic	0.815	pathogenic	-0.488	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
D/G	0.5548	ambiguous	0.4241	ambiguous	-0.717	Destabilizing	0.993	D	0.827	deleterious	N	0.456374337	None	None	N
D/H	0.7616	likely_pathogenic	0.6404	pathogenic	-0.901	Destabilizing	1.0	D	0.841	deleterious	N	0.486830148	None	None	N
D/I	0.8604	likely_pathogenic	0.7672	pathogenic	0.385	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
D/K	0.8947	likely_pathogenic	0.7823	pathogenic	-0.347	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
D/L	0.7347	likely_pathogenic	0.6137	pathogenic	0.385	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
D/M	0.9076	likely_pathogenic	0.8519	pathogenic	0.832	Stabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
D/N	0.2967	likely_benign	0.2206	benign	-0.616	Destabilizing	0.997	D	0.86	deleterious	N	0.520983176	None	None	N
D/P	0.9847	likely_pathogenic	0.9719	pathogenic	0.146	Stabilizing	0.995	D	0.861	deleterious	None	None	None	None	N
D/Q	0.7976	likely_pathogenic	0.6638	pathogenic	-0.521	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
D/R	0.9134	likely_pathogenic	0.8237	pathogenic	-0.357	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
D/S	0.3025	likely_benign	0.2119	benign	-0.852	Destabilizing	0.992	D	0.801	deleterious	None	None	None	None	N
D/T	0.7072	likely_pathogenic	0.565	pathogenic	-0.607	Destabilizing	0.997	D	0.873	deleterious	None	None	None	None	N
D/V	0.685	likely_pathogenic	0.5599	ambiguous	0.146	Stabilizing	0.998	D	0.878	deleterious	N	0.492906534	None	None	N
D/W	0.9837	likely_pathogenic	0.9729	pathogenic	-0.482	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
D/Y	0.6184	likely_pathogenic	0.4877	ambiguous	-0.288	Destabilizing	1.0	D	0.875	deleterious	N	0.486576658	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.