TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25225	75898;75899;75900	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
N2AB	23584	70975;70976;70977	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
N2A	22657	68194;68195;68196	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
N2B	16160	48703;48704;48705	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
Novex-1	16285	49078;49079;49080	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
Novex-2	16352	49279;49280;49281	chr2:178570459;178570458;178570457	chr2:179435186;179435185;179435184
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: Fn3-71
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.175
• 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	0.811	N	0.615	0.266	0.484329738948	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	2.78489E-05	None	0	0	0	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	0.2638	likely_benign	0.3248	benign	-0.682	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
A/D	0.2685	likely_benign	0.3209	benign	-0.976	Destabilizing	0.896	D	0.751	deleterious	N	0.518788233	None	None	N
A/E	0.2248	likely_benign	0.2546	benign	-0.904	Destabilizing	0.919	D	0.731	prob.delet.	None	None	None	None	N
A/F	0.1743	likely_benign	0.2039	benign	-0.602	Destabilizing	0.988	D	0.763	deleterious	None	None	None	None	N
A/G	0.1256	likely_benign	0.1391	benign	-1.014	Destabilizing	0.64	D	0.596	neutral	N	0.495892731	None	None	N
A/H	0.2765	likely_benign	0.3244	benign	-1.297	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
A/I	0.1493	likely_benign	0.1729	benign	0.206	Stabilizing	0.976	D	0.729	prob.delet.	None	None	None	None	N
A/K	0.3977	ambiguous	0.4445	ambiguous	-0.907	Destabilizing	0.919	D	0.737	prob.delet.	None	None	None	None	N
A/L	0.1019	likely_benign	0.1143	benign	0.206	Stabilizing	0.851	D	0.687	prob.neutral	None	None	None	None	N
A/M	0.1316	likely_benign	0.1541	benign	0.079	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
A/N	0.1688	likely_benign	0.198	benign	-0.88	Destabilizing	0.976	D	0.748	deleterious	None	None	None	None	N
A/P	0.8568	likely_pathogenic	0.903	pathogenic	-0.035	Destabilizing	0.984	D	0.73	prob.delet.	N	0.498956467	None	None	N
A/Q	0.2334	likely_benign	0.2626	benign	-0.849	Destabilizing	0.988	D	0.755	deleterious	None	None	None	None	N
A/R	0.3392	likely_benign	0.3834	ambiguous	-0.819	Destabilizing	0.976	D	0.728	prob.delet.	None	None	None	None	N
A/S	0.068	likely_benign	0.0724	benign	-1.308	Destabilizing	0.046	N	0.249	neutral	N	0.375329034	None	None	N
A/T	0.0657	likely_benign	0.0703	benign	-1.114	Destabilizing	0.103	N	0.463	neutral	N	0.453677962	None	None	N
A/V	0.0963	likely_benign	0.1084	benign	-0.035	Destabilizing	0.811	D	0.615	neutral	N	0.502069341	None	None	N
A/W	0.5066	ambiguous	0.5852	pathogenic	-1.156	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
A/Y	0.2547	likely_benign	0.3055	benign	-0.602	Destabilizing	0.996	D	0.771	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.