TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28097	84514;84515;84516	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
N2AB	26456	79591;79592;79593	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
N2A	25529	76810;76811;76812	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
N2B	19032	57319;57320;57321	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
Novex-1	19157	57694;57695;57696	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
Novex-2	19224	57895;57896;57897	chr2:178561843;178561842;178561841	chr2:179426570;179426569;179426568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-92
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.269
• 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
T/A	None	None	0.014	N	0.237	0.144	0.112648838833	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1296	likely_benign	0.1073	benign	-0.693	Destabilizing	0.014	N	0.237	neutral	N	0.445714626	None	None	N
T/C	0.6844	likely_pathogenic	0.5993	pathogenic	-0.381	Destabilizing	0.994	D	0.651	neutral	None	None	None	None	N
T/D	0.7491	likely_pathogenic	0.5812	pathogenic	-0.347	Destabilizing	0.956	D	0.572	neutral	None	None	None	None	N
T/E	0.6244	likely_pathogenic	0.4738	ambiguous	-0.392	Destabilizing	0.956	D	0.559	neutral	None	None	None	None	N
T/F	0.6911	likely_pathogenic	0.5168	ambiguous	-0.964	Destabilizing	0.978	D	0.732	prob.delet.	None	None	None	None	N
T/G	0.4356	ambiguous	0.3356	benign	-0.891	Destabilizing	0.754	D	0.635	neutral	None	None	None	None	N
T/H	0.6246	likely_pathogenic	0.4815	ambiguous	-1.207	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
T/I	0.3716	ambiguous	0.2641	benign	-0.269	Destabilizing	0.942	D	0.639	neutral	N	0.466533393	None	None	N
T/K	0.3646	ambiguous	0.2536	benign	-0.64	Destabilizing	0.956	D	0.568	neutral	None	None	None	None	N
T/L	0.1941	likely_benign	0.1468	benign	-0.269	Destabilizing	0.754	D	0.549	neutral	None	None	None	None	N
T/M	0.1177	likely_benign	0.099	benign	0.168	Stabilizing	0.998	D	0.648	neutral	None	None	None	None	N
T/N	0.2496	likely_benign	0.1584	benign	-0.478	Destabilizing	0.942	D	0.6	neutral	N	0.483734297	None	None	N
T/P	0.3806	ambiguous	0.3117	benign	-0.38	Destabilizing	0.971	D	0.645	neutral	N	0.506995159	None	None	N
T/Q	0.4457	ambiguous	0.3376	benign	-0.782	Destabilizing	0.956	D	0.643	neutral	None	None	None	None	N
T/R	0.3398	likely_benign	0.2262	benign	-0.283	Destabilizing	0.956	D	0.643	neutral	None	None	None	None	N
T/S	0.2291	likely_benign	0.1706	benign	-0.724	Destabilizing	0.058	N	0.279	neutral	N	0.465281822	None	None	N
T/V	0.2471	likely_benign	0.1913	benign	-0.38	Destabilizing	0.754	D	0.566	neutral	None	None	None	None	N
T/W	0.9201	likely_pathogenic	0.8488	pathogenic	-0.877	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
T/Y	0.6968	likely_pathogenic	0.53	ambiguous	-0.643	Destabilizing	0.993	D	0.729	prob.delet.	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.