TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14926	45001;45002;45003	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
N2AB	13285	40078;40079;40080	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
N2A	12358	37297;37298;37299	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
N2B	5861	17806;17807;17808	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
Novex-1	5986	18181;18182;18183	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
Novex-2	6053	18382;18383;18384	chr2:178624504;178624503;178624502	chr2:179489231;179489230;179489229
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-100
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.1357
• 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/V	None	None	0.998	D	0.685	0.592	0.540334051544	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.7397	likely_pathogenic	0.7857	pathogenic	-1.004	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/D	0.8918	likely_pathogenic	0.9362	pathogenic	-2.024	Highly Destabilizing	0.999	D	0.859	deleterious	D	0.803380118	None	None	N
A/E	0.8908	likely_pathogenic	0.9354	pathogenic	-1.943	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
A/F	0.823	likely_pathogenic	0.8914	pathogenic	-0.874	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
A/G	0.3452	ambiguous	0.4136	ambiguous	-1.479	Destabilizing	0.996	D	0.613	neutral	D	0.677009998	None	None	N
A/H	0.9281	likely_pathogenic	0.9489	pathogenic	-1.854	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/I	0.7062	likely_pathogenic	0.8067	pathogenic	-0.181	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/K	0.9531	likely_pathogenic	0.9777	pathogenic	-1.397	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
A/L	0.5883	likely_pathogenic	0.6964	pathogenic	-0.181	Destabilizing	0.998	D	0.746	deleterious	None	None	None	None	N
A/M	0.7272	likely_pathogenic	0.797	pathogenic	-0.195	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/N	0.8536	likely_pathogenic	0.8838	pathogenic	-1.332	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
A/P	0.9436	likely_pathogenic	0.9695	pathogenic	-0.447	Destabilizing	0.999	D	0.853	deleterious	D	0.688465899	None	None	N
A/Q	0.8774	likely_pathogenic	0.9217	pathogenic	-1.332	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/R	0.8741	likely_pathogenic	0.9275	pathogenic	-1.239	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/S	0.2217	likely_benign	0.2085	benign	-1.692	Destabilizing	0.957	D	0.373	neutral	D	0.623861126	None	None	N
A/T	0.3149	likely_benign	0.2845	benign	-1.514	Destabilizing	0.992	D	0.631	neutral	D	0.548730219	None	None	N
A/V	0.4228	ambiguous	0.4915	ambiguous	-0.447	Destabilizing	0.998	D	0.685	prob.neutral	D	0.527666501	None	None	N
A/W	0.9708	likely_pathogenic	0.9844	pathogenic	-1.488	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/Y	0.9129	likely_pathogenic	0.9504	pathogenic	-1.015	Destabilizing	1.0	D	0.876	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.