TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28744	86455;86456;86457	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
N2AB	27103	81532;81533;81534	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
N2A	26176	78751;78752;78753	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
N2B	19679	59260;59261;59262	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
Novex-1	19804	59635;59636;59637	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
Novex-2	19871	59836;59837;59838	chr2:178559902;178559901;178559900	chr2:179424629;179424628;179424627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-97
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.2563
• 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
I/M	None	None	0.177	N	0.499	0.017	0.220303561663	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
I/A	0.1284	likely_benign	0.1234	benign	-1.333	Destabilizing	0.016	N	0.507	neutral	None	None	None	None	N
I/C	0.4944	ambiguous	0.4837	ambiguous	-0.833	Destabilizing	0.685	D	0.485	neutral	None	None	None	None	N
I/D	0.4393	ambiguous	0.4248	ambiguous	-0.748	Destabilizing	0.366	N	0.685	prob.delet.	None	None	None	None	N
I/E	0.2804	likely_benign	0.2711	benign	-0.796	Destabilizing	0.366	N	0.654	prob.neutral	None	None	None	None	N
I/F	0.1143	likely_benign	0.107	benign	-1.043	Destabilizing	0.221	N	0.411	neutral	None	None	None	None	N
I/G	0.3821	ambiguous	0.3571	ambiguous	-1.591	Destabilizing	0.366	N	0.631	neutral	None	None	None	None	N
I/H	0.303	likely_benign	0.2923	benign	-0.737	Destabilizing	0.869	D	0.64	neutral	None	None	None	None	N
I/K	0.1845	likely_benign	0.1838	benign	-0.825	Destabilizing	0.303	N	0.647	neutral	N	0.45388860600000003	None	None	N
I/L	0.0877	likely_benign	0.0871	benign	-0.733	Destabilizing	None	N	0.075	neutral	N	0.446479844	None	None	N
I/M	0.0759	likely_benign	0.0745	benign	-0.534	Destabilizing	0.177	N	0.499	neutral	N	0.454061964	None	None	N
I/N	0.1754	likely_benign	0.1728	benign	-0.615	Destabilizing	0.637	D	0.657	prob.neutral	None	None	None	None	N
I/P	0.2816	likely_benign	0.2841	benign	-0.9	Destabilizing	0.637	D	0.693	prob.delet.	None	None	None	None	N
I/Q	0.2199	likely_benign	0.2125	benign	-0.864	Destabilizing	0.637	D	0.631	neutral	None	None	None	None	N
I/R	0.1532	likely_benign	0.1533	benign	-0.164	Destabilizing	0.303	N	0.669	prob.neutral	N	0.491233485	None	None	N
I/S	0.1611	likely_benign	0.1557	benign	-1.183	Destabilizing	0.075	N	0.597	neutral	None	None	None	None	N
I/T	0.0815	likely_benign	0.0794	benign	-1.121	Destabilizing	0.03	N	0.538	neutral	N	0.408009095	None	None	N
I/V	0.0583	likely_benign	0.0578	benign	-0.9	Destabilizing	None	N	0.063	neutral	N	0.381295002	None	None	N
I/W	0.584	likely_pathogenic	0.5539	ambiguous	-1.046	Destabilizing	0.869	D	0.691	prob.delet.	None	None	None	None	N
I/Y	0.3468	ambiguous	0.3242	benign	-0.827	Destabilizing	0.366	N	0.536	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.