TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17461	52606;52607;52608	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
N2AB	15820	47683;47684;47685	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
N2A	14893	44902;44903;44904	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
N2B	8396	25411;25412;25413	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
Novex-1	8521	25786;25787;25788	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
Novex-2	8588	25987;25988;25989	chr2:178608630;178608629;178608628	chr2:179473357;179473356;179473355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-14
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.3542
• 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/S	rs2055511936	None	0.995	N	0.805	0.283	0.258779203287	gnomAD-4.0.0	1.59742E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86618E-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	0.0906	likely_benign	0.092	benign	-1.068	Destabilizing	0.603	D	0.403	neutral	N	0.471454009	None	None	N
P/C	0.5147	ambiguous	0.503	ambiguous	-0.793	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/D	0.5189	ambiguous	0.5146	ambiguous	-0.793	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/E	0.3486	ambiguous	0.3452	ambiguous	-0.788	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
P/F	0.5802	likely_pathogenic	0.5906	pathogenic	-0.747	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/G	0.3728	ambiguous	0.3642	ambiguous	-1.353	Destabilizing	0.993	D	0.788	deleterious	None	None	None	None	N
P/H	0.3276	likely_benign	0.3079	benign	-0.693	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/I	0.3301	likely_benign	0.331	benign	-0.396	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
P/K	0.4876	ambiguous	0.4611	ambiguous	-0.938	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
P/L	0.1695	likely_benign	0.1658	benign	-0.396	Destabilizing	0.997	D	0.755	deleterious	N	0.49391313	None	None	N
P/M	0.3686	ambiguous	0.3678	ambiguous	-0.468	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/N	0.4017	ambiguous	0.3987	ambiguous	-0.814	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/Q	0.2907	likely_benign	0.275	benign	-0.935	Destabilizing	1.0	D	0.852	deleterious	N	0.488597212	None	None	N
P/R	0.3678	ambiguous	0.34	benign	-0.441	Destabilizing	0.999	D	0.857	deleterious	N	0.474607561	None	None	N
P/S	0.1658	likely_benign	0.1654	benign	-1.3	Destabilizing	0.995	D	0.805	deleterious	N	0.521825751	None	None	N
P/T	0.1509	likely_benign	0.1478	benign	-1.179	Destabilizing	0.997	D	0.767	deleterious	N	0.46897202	None	None	N
P/V	0.2124	likely_benign	0.2141	benign	-0.586	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
P/W	0.7504	likely_pathogenic	0.7458	pathogenic	-0.916	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/Y	0.536	ambiguous	0.5336	ambiguous	-0.611	Destabilizing	1.0	D	0.867	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.