TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13836	41731;41732;41733	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
N2AB	12195	36808;36809;36810	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
N2A	11268	34027;34028;34029	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
N2B	4771	14536;14537;14538	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
Novex-1	4896	14911;14912;14913	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
Novex-2	4963	15112;15113;15114	chr2:178636065;178636064;178636063	chr2:179500792;179500791;179500790
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-88
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1484
• 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	rs1326857970	-1.74	0.007	N	0.302	0.042	0.0986583533028	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/S	rs1326857970	-1.74	0.007	N	0.302	0.042	0.0986583533028	gnomAD-4.0.0	1.59232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86002E-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	0.6792	likely_pathogenic	0.649	pathogenic	-0.92	Destabilizing	0.992	D	0.671	prob.neutral	None	None	None	None	N
A/D	0.9239	likely_pathogenic	0.9458	pathogenic	-1.71	Destabilizing	0.549	D	0.712	prob.delet.	N	0.344593131	None	None	N
A/E	0.8466	likely_pathogenic	0.8833	pathogenic	-1.592	Destabilizing	0.617	D	0.723	deleterious	None	None	None	None	N
A/F	0.6298	likely_pathogenic	0.6658	pathogenic	-0.758	Destabilizing	0.739	D	0.729	deleterious	None	None	None	None	N
A/G	0.3862	ambiguous	0.4218	ambiguous	-1.317	Destabilizing	0.201	N	0.685	prob.delet.	N	0.338988895	None	None	N
A/H	0.8721	likely_pathogenic	0.8817	pathogenic	-1.803	Destabilizing	0.92	D	0.719	prob.delet.	None	None	None	None	N
A/I	0.5776	likely_pathogenic	0.5935	pathogenic	0.181	Stabilizing	0.217	N	0.727	deleterious	None	None	None	None	N
A/K	0.9386	likely_pathogenic	0.9586	pathogenic	-1.091	Destabilizing	0.617	D	0.729	deleterious	None	None	None	None	N
A/L	0.4868	ambiguous	0.481	ambiguous	0.181	Stabilizing	0.25	N	0.713	prob.delet.	None	None	None	None	N
A/M	0.5017	ambiguous	0.4942	ambiguous	0.074	Stabilizing	0.85	D	0.689	prob.delet.	None	None	None	None	N
A/N	0.7411	likely_pathogenic	0.7674	pathogenic	-1.117	Destabilizing	0.85	D	0.711	prob.delet.	None	None	None	None	N
A/P	0.9589	likely_pathogenic	0.9747	pathogenic	-0.132	Destabilizing	0.896	D	0.738	deleterious	N	0.312275965	None	None	N
A/Q	0.7964	likely_pathogenic	0.8143	pathogenic	-1.039	Destabilizing	0.92	D	0.765	deleterious	None	None	None	None	N
A/R	0.8648	likely_pathogenic	0.9019	pathogenic	-1.098	Destabilizing	0.85	D	0.747	deleterious	None	None	None	None	N
A/S	0.1733	likely_benign	0.1695	benign	-1.536	Destabilizing	0.007	N	0.302	neutral	N	0.32753983	None	None	N
A/T	0.227	likely_benign	0.2376	benign	-1.293	Destabilizing	0.002	N	0.291	neutral	N	0.338672212	None	None	N
A/V	0.3069	likely_benign	0.316	benign	-0.132	Destabilizing	0.004	N	0.463	neutral	N	0.346677199	None	None	N
A/W	0.9448	likely_pathogenic	0.9539	pathogenic	-1.427	Destabilizing	0.992	D	0.767	deleterious	None	None	None	None	N
A/Y	0.7822	likely_pathogenic	0.8087	pathogenic	-0.864	Destabilizing	0.048	N	0.573	neutral	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.