TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7680	23263;23264;23265	chr2:178720981;178720980;178720979	chr2:179585708;179585707;179585706
N2AB	7363	22312;22313;22314	chr2:178720981;178720980;178720979	chr2:179585708;179585707;179585706
N2A	6436	19531;19532;19533	chr2:178720981;178720980;178720979	chr2:179585708;179585707;179585706
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-61
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.1406
• 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/L	None	None	0.267	N	0.431	0.105	0.462461958149	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
I/V	None	None	0.267	N	0.409	0.059	0.33340067248	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.4036	ambiguous	0.4908	ambiguous	-2.309	Highly Destabilizing	0.525	D	0.549	neutral	None	None	None	None	N
I/C	0.7648	likely_pathogenic	0.8	pathogenic	-1.933	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
I/D	0.7713	likely_pathogenic	0.8722	pathogenic	-2.129	Highly Destabilizing	0.949	D	0.632	neutral	None	None	None	None	N
I/E	0.6824	likely_pathogenic	0.8046	pathogenic	-1.973	Destabilizing	0.842	D	0.614	neutral	None	None	None	None	N
I/F	0.1658	likely_benign	0.225	benign	-1.45	Destabilizing	0.669	D	0.591	neutral	N	0.488531536	None	None	N
I/G	0.7133	likely_pathogenic	0.8052	pathogenic	-2.782	Highly Destabilizing	0.842	D	0.592	neutral	None	None	None	None	N
I/H	0.4433	ambiguous	0.609	pathogenic	-2.075	Highly Destabilizing	0.949	D	0.663	neutral	None	None	None	None	N
I/K	0.3991	ambiguous	0.6007	pathogenic	-1.535	Destabilizing	0.842	D	0.619	neutral	None	None	None	None	N
I/L	0.1484	likely_benign	0.1821	benign	-0.979	Destabilizing	0.267	N	0.431	neutral	N	0.453090811	None	None	N
I/M	0.1377	likely_benign	0.1657	benign	-1.085	Destabilizing	0.989	D	0.621	neutral	N	0.45243745	None	None	N
I/N	0.3376	likely_benign	0.4409	ambiguous	-1.684	Destabilizing	0.934	D	0.629	neutral	N	0.510157602	None	None	N
I/P	0.971	likely_pathogenic	0.9826	pathogenic	-1.4	Destabilizing	0.974	D	0.62	neutral	None	None	None	None	N
I/Q	0.483	ambiguous	0.6325	pathogenic	-1.67	Destabilizing	0.974	D	0.633	neutral	None	None	None	None	N
I/R	0.2781	likely_benign	0.4584	ambiguous	-1.207	Destabilizing	0.974	D	0.618	neutral	None	None	None	None	N
I/S	0.2623	likely_benign	0.3228	benign	-2.469	Highly Destabilizing	0.669	D	0.61	neutral	N	0.435966488	None	None	N
I/T	0.1766	likely_benign	0.2156	benign	-2.172	Highly Destabilizing	0.022	N	0.399	neutral	N	0.344765693	None	None	N
I/V	0.0918	likely_benign	0.0964	benign	-1.4	Destabilizing	0.267	N	0.409	neutral	N	0.416823366	None	None	N
I/W	0.7436	likely_pathogenic	0.8425	pathogenic	-1.651	Destabilizing	0.993	D	0.675	neutral	None	None	None	None	N
I/Y	0.4705	ambiguous	0.6089	pathogenic	-1.402	Destabilizing	0.029	N	0.401	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.