TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32449	97570;97571;97572	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
N2AB	30808	92647;92648;92649	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
N2A	29881	89866;89867;89868	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
N2B	23384	70375;70376;70377	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
Novex-1	23509	70750;70751;70752	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
Novex-2	23576	70951;70952;70953	chr2:178542411;178542410;178542409	chr2:179407138;179407137;179407136
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: Fn3-124
• Domain position: 51
• Structural Position: 67
• Q(SASA): 0.4299
• 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	rs1248314451	None	0.122	N	0.275	0.257	0.243398259712	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/T	rs1248314451	None	0.122	N	0.275	0.257	0.243398259712	gnomAD-4.0.0	9.91631E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35627E-05	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	0.1157	likely_benign	0.1118	benign	-0.767	Destabilizing	0.835	D	0.425	neutral	N	0.431995968	None	None	N
P/C	0.6614	likely_pathogenic	0.6361	pathogenic	-0.697	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
P/D	0.8328	likely_pathogenic	0.8519	pathogenic	-0.684	Destabilizing	0.97	D	0.491	neutral	None	None	None	None	N
P/E	0.6148	likely_pathogenic	0.6303	pathogenic	-0.783	Destabilizing	0.97	D	0.485	neutral	None	None	None	None	N
P/F	0.7628	likely_pathogenic	0.7628	pathogenic	-0.821	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
P/G	0.4809	ambiguous	0.4965	ambiguous	-0.942	Destabilizing	0.97	D	0.532	neutral	None	None	None	None	N
P/H	0.4363	ambiguous	0.4413	ambiguous	-0.446	Destabilizing	1.0	D	0.649	neutral	N	0.496410019	None	None	N
P/I	0.4486	ambiguous	0.4271	ambiguous	-0.441	Destabilizing	0.991	D	0.653	neutral	None	None	None	None	N
P/K	0.6581	likely_pathogenic	0.6618	pathogenic	-0.758	Destabilizing	0.97	D	0.485	neutral	None	None	None	None	N
P/L	0.1894	likely_benign	0.1858	benign	-0.441	Destabilizing	0.961	D	0.568	neutral	N	0.419394817	None	None	N
P/M	0.434	ambiguous	0.4204	ambiguous	-0.421	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
P/N	0.5713	likely_pathogenic	0.5863	pathogenic	-0.471	Destabilizing	0.991	D	0.603	neutral	None	None	None	None	N
P/Q	0.3314	likely_benign	0.3306	benign	-0.739	Destabilizing	0.996	D	0.614	neutral	None	None	None	None	N
P/R	0.4797	ambiguous	0.467	ambiguous	-0.152	Destabilizing	0.994	D	0.642	neutral	N	0.427339509	None	None	N
P/S	0.2453	likely_benign	0.2517	benign	-0.835	Destabilizing	0.489	N	0.319	neutral	N	0.445231837	None	None	N
P/T	0.1702	likely_benign	0.1729	benign	-0.837	Destabilizing	0.122	N	0.275	neutral	N	0.337853656	None	None	N
P/V	0.2844	likely_benign	0.2732	benign	-0.514	Destabilizing	0.97	D	0.549	neutral	None	None	None	None	N
P/W	0.886	likely_pathogenic	0.8831	pathogenic	-0.898	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
P/Y	0.7405	likely_pathogenic	0.7323	pathogenic	-0.629	Destabilizing	0.999	D	0.68	prob.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.