TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19897	59914;59915;59916	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
N2AB	18256	54991;54992;54993	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
N2A	17329	52210;52211;52212	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
N2B	10832	32719;32720;32721	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
Novex-1	10957	33094;33095;33096	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
Novex-2	11024	33295;33296;33297	chr2:178592215;178592214;178592213	chr2:179456942;179456941;179456940
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-32
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2338
• 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/P	None	None	0.994	N	0.629	0.435	0.516827169674	gnomAD-4.0.0	3.19186E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.87439E-05	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	0.1143	likely_benign	0.1292	benign	-1.05	Destabilizing	0.835	D	0.405	neutral	N	0.485177092	None	None	N
T/C	0.4042	ambiguous	0.4407	ambiguous	-0.487	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.631	likely_pathogenic	0.6624	pathogenic	-0.922	Destabilizing	0.97	D	0.562	neutral	None	None	None	None	N
T/E	0.4964	ambiguous	0.5304	ambiguous	-0.736	Destabilizing	0.97	D	0.548	neutral	None	None	None	None	N
T/F	0.2851	likely_benign	0.2988	benign	-0.708	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
T/G	0.3316	likely_benign	0.3659	ambiguous	-1.443	Destabilizing	0.97	D	0.515	neutral	None	None	None	None	N
T/H	0.2337	likely_benign	0.2627	benign	-1.482	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/I	0.2019	likely_benign	0.2207	benign	-0.02	Destabilizing	0.994	D	0.628	neutral	N	0.477119684	None	None	N
T/K	0.2338	likely_benign	0.273	benign	-0.213	Destabilizing	0.97	D	0.557	neutral	None	None	None	None	N
T/L	0.114	likely_benign	0.1237	benign	-0.02	Destabilizing	0.985	D	0.485	neutral	None	None	None	None	N
T/M	0.0967	likely_benign	0.1004	benign	-0.109	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
T/N	0.154	likely_benign	0.1651	benign	-0.75	Destabilizing	0.961	D	0.525	neutral	N	0.503416136	None	None	N
T/P	0.782	likely_pathogenic	0.8373	pathogenic	-0.333	Destabilizing	0.994	D	0.629	neutral	N	0.50361773	None	None	N
T/Q	0.2174	likely_benign	0.2471	benign	-0.563	Destabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	N
T/R	0.2065	likely_benign	0.2423	benign	-0.42	Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
T/S	0.1184	likely_benign	0.1258	benign	-1.025	Destabilizing	0.287	N	0.281	neutral	N	0.395301662	None	None	N
T/V	0.1656	likely_benign	0.1779	benign	-0.333	Destabilizing	0.985	D	0.456	neutral	None	None	None	None	N
T/W	0.6661	likely_pathogenic	0.6789	pathogenic	-0.829	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
T/Y	0.3341	likely_benign	0.3557	ambiguous	-0.446	Destabilizing	0.999	D	0.763	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.