TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19929	60010;60011;60012	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
N2AB	18288	55087;55088;55089	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
N2A	17361	52306;52307;52308	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
N2B	10864	32815;32816;32817	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
Novex-1	10989	33190;33191;33192	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
Novex-2	11056	33391;33392;33393	chr2:178592119;178592118;178592117	chr2:179456846;179456845;179456844
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: Fn3-32
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.5428
• 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	rs777824631	0.239	0.012	N	0.221	0.166	0.229924730088	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
A/C	0.2914	likely_benign	0.2663	benign	-0.813	Destabilizing	0.356	N	0.325	neutral	None	None	None	None	N
A/D	0.3102	likely_benign	0.3003	benign	-0.623	Destabilizing	0.024	N	0.292	neutral	N	0.4505258	None	None	N
A/E	0.2937	likely_benign	0.2872	benign	-0.773	Destabilizing	0.031	N	0.295	neutral	None	None	None	None	N
A/F	0.2372	likely_benign	0.2323	benign	-1.092	Destabilizing	0.356	N	0.361	neutral	None	None	None	None	N
A/G	0.115	likely_benign	0.1051	benign	-0.494	Destabilizing	0.012	N	0.218	neutral	N	0.486505243	None	None	N
A/H	0.3498	ambiguous	0.3198	benign	-0.536	Destabilizing	0.628	D	0.301	neutral	None	None	None	None	N
A/I	0.1461	likely_benign	0.141	benign	-0.452	Destabilizing	0.038	N	0.273	neutral	None	None	None	None	N
A/K	0.4086	ambiguous	0.3874	ambiguous	-0.607	Destabilizing	0.031	N	0.299	neutral	None	None	None	None	N
A/L	0.1114	likely_benign	0.1035	benign	-0.452	Destabilizing	0.016	N	0.321	neutral	None	None	None	None	N
A/M	0.138	likely_benign	0.1237	benign	-0.325	Destabilizing	0.356	N	0.319	neutral	None	None	None	None	N
A/N	0.1493	likely_benign	0.1319	benign	-0.328	Destabilizing	0.031	N	0.292	neutral	None	None	None	None	N
A/P	0.1018	likely_benign	0.0939	benign	-0.411	Destabilizing	0.106	N	0.273	neutral	N	0.475096171	None	None	N
A/Q	0.2712	likely_benign	0.2536	benign	-0.654	Destabilizing	0.136	N	0.343	neutral	None	None	None	None	N
A/R	0.4034	ambiguous	0.3835	ambiguous	-0.143	Destabilizing	0.072	N	0.338	neutral	None	None	None	None	N
A/S	0.0803	likely_benign	0.0778	benign	-0.551	Destabilizing	None	N	0.082	neutral	N	0.402214565	None	None	N
A/T	0.0655	likely_benign	0.063	benign	-0.625	Destabilizing	None	N	0.072	neutral	N	0.424051275	None	None	N
A/V	0.0918	likely_benign	0.0894	benign	-0.411	Destabilizing	0.012	N	0.221	neutral	N	0.483112648	None	None	N
A/W	0.5735	likely_pathogenic	0.5676	pathogenic	-1.206	Destabilizing	0.864	D	0.324	neutral	None	None	None	None	N
A/Y	0.3238	likely_benign	0.3183	benign	-0.84	Destabilizing	0.356	N	0.329	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.