TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23019	69280;69281;69282	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
N2AB	21378	64357;64358;64359	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
N2A	20451	61576;61577;61578	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
N2B	13954	42085;42086;42087	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
Novex-1	14079	42460;42461;42462	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
Novex-2	14146	42661;42662;42663	chr2:178577280;178577279;178577278	chr2:179442007;179442006;179442005
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-128
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.1697
• 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/I	None	None	0.125	N	0.448	0.146	0.339555952218	gnomAD-4.0.0	3.1848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71971E-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
T/A	0.1061	likely_benign	0.0997	benign	-1.242	Destabilizing	0.656	D	0.581	neutral	N	0.473332751	None	None	N
T/C	0.3653	ambiguous	0.3404	ambiguous	-0.927	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	N
T/D	0.483	ambiguous	0.4642	ambiguous	-1.787	Destabilizing	0.956	D	0.675	neutral	None	None	None	None	N
T/E	0.3148	likely_benign	0.2973	benign	-1.546	Destabilizing	0.754	D	0.637	neutral	None	None	None	None	N
T/F	0.2807	likely_benign	0.2555	benign	-0.932	Destabilizing	0.978	D	0.738	prob.delet.	None	None	None	None	N
T/G	0.3642	ambiguous	0.3353	benign	-1.669	Destabilizing	0.956	D	0.675	neutral	None	None	None	None	N
T/H	0.2958	likely_benign	0.2794	benign	-1.753	Destabilizing	0.994	D	0.727	prob.delet.	None	None	None	None	N
T/I	0.1448	likely_benign	0.1238	benign	-0.103	Destabilizing	0.125	N	0.448	neutral	N	0.455873606	None	None	N
T/K	0.2697	likely_benign	0.2447	benign	-0.343	Destabilizing	0.915	D	0.651	neutral	None	None	None	None	N
T/L	0.1173	likely_benign	0.1144	benign	-0.103	Destabilizing	0.754	D	0.625	neutral	None	None	None	None	N
T/M	0.0909	likely_benign	0.0865	benign	-0.221	Destabilizing	0.978	D	0.708	prob.delet.	None	None	None	None	N
T/N	0.1743	likely_benign	0.1643	benign	-1.207	Destabilizing	0.942	D	0.581	neutral	N	0.4827405	None	None	N
T/P	0.8313	likely_pathogenic	0.8503	pathogenic	-0.453	Destabilizing	0.97	D	0.71	prob.delet.	N	0.51245455	None	None	N
T/Q	0.2397	likely_benign	0.2309	benign	-0.903	Destabilizing	0.16	N	0.495	neutral	None	None	None	None	N
T/R	0.2145	likely_benign	0.1984	benign	-0.684	Destabilizing	0.915	D	0.696	prob.neutral	None	None	None	None	N
T/S	0.1235	likely_benign	0.1205	benign	-1.407	Destabilizing	0.822	D	0.568	neutral	N	0.494729577	None	None	N
T/V	0.1207	likely_benign	0.1095	benign	-0.453	Destabilizing	0.754	D	0.581	neutral	None	None	None	None	N
T/W	0.6597	likely_pathogenic	0.6495	pathogenic	-1.139	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
T/Y	0.3321	likely_benign	0.3179	benign	-0.718	Destabilizing	0.993	D	0.749	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.