TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6078	18457;18458;18459	chr2:178730168;178730167;178730166	chr2:179594895;179594894;179594893
N2AB	5761	17506;17507;17508	chr2:178730168;178730167;178730166	chr2:179594895;179594894;179594893
N2A	4834	14725;14726;14727	chr2:178730168;178730167;178730166	chr2:179594895;179594894;179594893
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-44
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2627
• 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/N	rs748917636	-0.305	0.837	D	0.714	0.546	0.457741393631	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	0	None	0	1.0304E-04	None	0	None	8.01E-05	2.35E-05	0
D/N	rs748917636	-0.305	0.837	D	0.714	0.546	0.457741393631	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	9.44E-05	0	2.94E-05	0	0
D/N	rs748917636	-0.305	0.837	D	0.714	0.546	0.457741393631	gnomAD-4.0.0	1.42571E-05	None	None	None	None	N	None	1.33558E-05	1.66889E-05	None	0	1.3397E-04	None	3.12607E-05	0	1.10203E-05	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	0.8565	likely_pathogenic	0.7514	pathogenic	-0.042	Destabilizing	0.645	D	0.822	deleterious	D	0.612994591	None	None	N
D/C	0.9685	likely_pathogenic	0.9456	pathogenic	0.023	Stabilizing	0.995	D	0.825	deleterious	None	None	None	None	N
D/E	0.7177	likely_pathogenic	0.6431	pathogenic	-0.694	Destabilizing	0.477	N	0.639	neutral	D	0.61851654	None	None	N
D/F	0.98	likely_pathogenic	0.9553	pathogenic	0.655	Stabilizing	0.809	D	0.839	deleterious	None	None	None	None	N
D/G	0.9124	likely_pathogenic	0.86	pathogenic	-0.47	Destabilizing	0.645	D	0.771	deleterious	D	0.645467282	None	None	N
D/H	0.8141	likely_pathogenic	0.6853	pathogenic	0.305	Stabilizing	0.071	N	0.57	neutral	D	0.58994957	None	None	N
D/I	0.9677	likely_pathogenic	0.932	pathogenic	1.101	Stabilizing	0.945	D	0.841	deleterious	None	None	None	None	N
D/K	0.9724	likely_pathogenic	0.9484	pathogenic	0.027	Stabilizing	0.894	D	0.791	deleterious	None	None	None	None	N
D/L	0.9675	likely_pathogenic	0.932	pathogenic	1.101	Stabilizing	0.894	D	0.836	deleterious	None	None	None	None	N
D/M	0.9839	likely_pathogenic	0.9632	pathogenic	1.475	Stabilizing	0.995	D	0.82	deleterious	None	None	None	None	N
D/N	0.602	likely_pathogenic	0.4954	ambiguous	-0.757	Destabilizing	0.837	D	0.714	prob.delet.	D	0.585842045	None	None	N
D/P	0.9947	likely_pathogenic	0.9893	pathogenic	0.749	Stabilizing	0.945	D	0.783	deleterious	None	None	None	None	N
D/Q	0.9175	likely_pathogenic	0.8476	pathogenic	-0.487	Destabilizing	0.894	D	0.743	deleterious	None	None	None	None	N
D/R	0.9758	likely_pathogenic	0.9551	pathogenic	0.141	Stabilizing	0.894	D	0.838	deleterious	None	None	None	None	N
D/S	0.7341	likely_pathogenic	0.6184	pathogenic	-0.977	Destabilizing	0.707	D	0.705	prob.neutral	None	None	None	None	N
D/T	0.9325	likely_pathogenic	0.8812	pathogenic	-0.591	Destabilizing	0.945	D	0.791	deleterious	None	None	None	None	N
D/V	0.9134	likely_pathogenic	0.8393	pathogenic	0.749	Stabilizing	0.864	D	0.841	deleterious	D	0.645870891	None	None	N
D/W	0.996	likely_pathogenic	0.991	pathogenic	0.827	Stabilizing	0.995	D	0.823	deleterious	None	None	None	None	N
D/Y	0.8669	likely_pathogenic	0.7796	pathogenic	0.932	Stabilizing	0.125	N	0.643	neutral	D	0.629417561	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.