TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26529	79810;79811;79812	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
N2AB	24888	74887;74888;74889	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
N2A	23961	72106;72107;72108	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
N2B	17464	52615;52616;52617	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
Novex-1	17589	52990;52991;52992	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
Novex-2	17656	53191;53192;53193	chr2:178566547;178566546;178566545	chr2:179431274;179431273;179431272
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-81
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2598
• 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/T	None	None	0.822	N	0.545	0.225	0.304108284078	gnomAD-4.0.0	4.10648E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49757E-06	0	1.65695E-05

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	0.5017	ambiguous	0.5323	ambiguous	-0.998	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
A/D	0.2375	likely_benign	0.2496	benign	-1.715	Destabilizing	0.915	D	0.555	neutral	None	None	None	None	N
A/E	0.1969	likely_benign	0.2086	benign	-1.799	Destabilizing	0.032	N	0.33	neutral	N	0.458662494	None	None	N
A/F	0.408	ambiguous	0.4234	ambiguous	-1.358	Destabilizing	0.956	D	0.633	neutral	None	None	None	None	N
A/G	0.1127	likely_benign	0.1207	benign	-1.278	Destabilizing	0.014	N	0.323	neutral	N	0.454200824	None	None	N
A/H	0.5234	ambiguous	0.5551	ambiguous	-1.257	Destabilizing	0.994	D	0.627	neutral	None	None	None	None	N
A/I	0.1891	likely_benign	0.1954	benign	-0.732	Destabilizing	0.915	D	0.507	neutral	None	None	None	None	N
A/K	0.3641	ambiguous	0.4071	ambiguous	-1.349	Destabilizing	0.915	D	0.508	neutral	None	None	None	None	N
A/L	0.1836	likely_benign	0.1967	benign	-0.732	Destabilizing	0.754	D	0.513	neutral	None	None	None	None	N
A/M	0.1908	likely_benign	0.2083	benign	-0.436	Destabilizing	0.994	D	0.57	neutral	None	None	None	None	N
A/N	0.2273	likely_benign	0.2393	benign	-1.049	Destabilizing	0.956	D	0.621	neutral	None	None	None	None	N
A/P	0.186	likely_benign	0.2101	benign	-0.813	Destabilizing	0.97	D	0.571	neutral	N	0.459684001	None	None	N
A/Q	0.3265	likely_benign	0.3574	ambiguous	-1.351	Destabilizing	0.915	D	0.566	neutral	None	None	None	None	N
A/R	0.4056	ambiguous	0.4477	ambiguous	-0.782	Destabilizing	0.956	D	0.568	neutral	None	None	None	None	N
A/S	0.1006	likely_benign	0.1027	benign	-1.309	Destabilizing	0.822	D	0.55	neutral	N	0.463761669	None	None	N
A/T	0.087	likely_benign	0.0891	benign	-1.324	Destabilizing	0.822	D	0.545	neutral	N	0.489542761	None	None	N
A/V	0.1056	likely_benign	0.1059	benign	-0.813	Destabilizing	0.032	N	0.251	neutral	N	0.442866322	None	None	N
A/W	0.7356	likely_pathogenic	0.7788	pathogenic	-1.58	Destabilizing	0.998	D	0.65	neutral	None	None	None	None	N
A/Y	0.4915	ambiguous	0.5245	ambiguous	-1.256	Destabilizing	0.978	D	0.634	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.