TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27455	82588;82589;82590	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
N2AB	25814	77665;77666;77667	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
N2A	24887	74884;74885;74886	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
N2B	18390	55393;55394;55395	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
Novex-1	18515	55768;55769;55770	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
Novex-2	18582	55969;55970;55971	chr2:178563769;178563768;178563767	chr2:179428496;179428495;179428494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-87
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2939
• 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
P/T	None	None	0.709	D	0.637	0.251	0.292787519742	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85845E-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
P/A	0.0941	likely_benign	0.0878	benign	-1.76	Destabilizing	0.004	N	0.347	neutral	N	0.465048454	None	None	N
P/C	0.5312	ambiguous	0.5246	ambiguous	-0.916	Destabilizing	0.98	D	0.803	deleterious	None	None	None	None	N
P/D	0.8315	likely_pathogenic	0.8159	pathogenic	-1.942	Destabilizing	0.866	D	0.689	prob.neutral	None	None	None	None	N
P/E	0.6917	likely_pathogenic	0.6524	pathogenic	-1.932	Destabilizing	0.866	D	0.623	neutral	None	None	None	None	N
P/F	0.5511	ambiguous	0.5628	ambiguous	-1.343	Destabilizing	0.98	D	0.807	deleterious	None	None	None	None	N
P/G	0.4259	ambiguous	0.4248	ambiguous	-2.08	Highly Destabilizing	0.48	N	0.583	neutral	None	None	None	None	N
P/H	0.4064	ambiguous	0.4111	ambiguous	-1.642	Destabilizing	0.991	D	0.772	deleterious	D	0.529289174	None	None	N
P/I	0.5394	ambiguous	0.4973	ambiguous	-0.956	Destabilizing	0.866	D	0.766	deleterious	None	None	None	None	N
P/K	0.732	likely_pathogenic	0.7032	pathogenic	-1.498	Destabilizing	0.866	D	0.629	neutral	None	None	None	None	N
P/L	0.3367	likely_benign	0.3277	benign	-0.956	Destabilizing	0.709	D	0.686	prob.neutral	N	0.515397973	None	None	N
P/M	0.5045	ambiguous	0.4867	ambiguous	-0.602	Destabilizing	0.98	D	0.777	deleterious	None	None	None	None	N
P/N	0.6481	likely_pathogenic	0.6351	pathogenic	-1.266	Destabilizing	0.929	D	0.763	deleterious	None	None	None	None	N
P/Q	0.4766	ambiguous	0.448	ambiguous	-1.46	Destabilizing	0.929	D	0.743	deleterious	None	None	None	None	N
P/R	0.5943	likely_pathogenic	0.5781	pathogenic	-0.889	Destabilizing	0.83	D	0.744	deleterious	N	0.513133475	None	None	N
P/S	0.2082	likely_benign	0.1892	benign	-1.713	Destabilizing	0.41	N	0.554	neutral	N	0.485634698	None	None	N
P/T	0.2605	likely_benign	0.2359	benign	-1.614	Destabilizing	0.709	D	0.637	neutral	D	0.528528705	None	None	N
P/V	0.3751	ambiguous	0.3405	ambiguous	-1.193	Destabilizing	0.764	D	0.648	neutral	None	None	None	None	N
P/W	0.7378	likely_pathogenic	0.7387	pathogenic	-1.592	Destabilizing	0.993	D	0.792	deleterious	None	None	None	None	N
P/Y	0.5159	ambiguous	0.5192	ambiguous	-1.333	Destabilizing	0.98	D	0.802	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.