TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8804	26635;26636;26637	chr2:178714364;178714363;178714362	chr2:179579091;179579090;179579089
N2AB	8487	25684;25685;25686	chr2:178714364;178714363;178714362	chr2:179579091;179579090;179579089
N2A	7560	22903;22904;22905	chr2:178714364;178714363;178714362	chr2:179579091;179579090;179579089
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-73
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2411
• 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
A/P	rs778012263	None	0.384	D	0.684	0.333	0.339074221408	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/P	rs778012263	None	0.384	D	0.684	0.333	0.339074221408	gnomAD-4.0.0	1.85913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.5429E-06	0	0
A/S	rs778012263	-0.952	None	N	0.348	0.05	0.18274738541	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	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
A/C	0.4689	ambiguous	0.4945	ambiguous	-0.823	Destabilizing	0.863	D	0.559	neutral	None	None	None	None	N
A/D	0.2583	likely_benign	0.3119	benign	-0.469	Destabilizing	0.238	N	0.664	neutral	D	0.535483774	None	None	N
A/E	0.2064	likely_benign	0.2321	benign	-0.567	Destabilizing	0.366	N	0.629	neutral	None	None	None	None	N
A/F	0.2865	likely_benign	0.3394	benign	-0.985	Destabilizing	0.862	D	0.759	deleterious	None	None	None	None	N
A/G	0.1149	likely_benign	0.1266	benign	-0.786	Destabilizing	0.009	N	0.434	neutral	N	0.51724473	None	None	N
A/H	0.4199	ambiguous	0.4527	ambiguous	-0.864	Destabilizing	0.959	D	0.733	prob.delet.	None	None	None	None	N
A/I	0.1869	likely_benign	0.2404	benign	-0.361	Destabilizing	0.607	D	0.685	prob.neutral	None	None	None	None	N
A/K	0.3275	likely_benign	0.3796	ambiguous	-0.841	Destabilizing	0.607	D	0.632	neutral	None	None	None	None	N
A/L	0.1622	likely_benign	0.1919	benign	-0.361	Destabilizing	0.306	N	0.545	neutral	None	None	None	None	N
A/M	0.1671	likely_benign	0.2004	benign	-0.32	Destabilizing	0.959	D	0.667	neutral	None	None	None	None	N
A/N	0.2313	likely_benign	0.2693	benign	-0.514	Destabilizing	0.046	N	0.723	prob.delet.	None	None	None	None	N
A/P	0.5233	ambiguous	0.6362	pathogenic	-0.409	Destabilizing	0.384	N	0.684	prob.neutral	D	0.528741829	None	None	N
A/Q	0.2869	likely_benign	0.3063	benign	-0.733	Destabilizing	0.755	D	0.697	prob.neutral	None	None	None	None	N
A/R	0.2794	likely_benign	0.3186	benign	-0.462	Destabilizing	0.755	D	0.693	prob.neutral	None	None	None	None	N
A/S	0.0896	likely_benign	0.0889	benign	-0.858	Destabilizing	None	N	0.348	neutral	N	0.461137944	None	None	N
A/T	0.0768	likely_benign	0.0861	benign	-0.86	Destabilizing	None	N	0.242	neutral	D	0.525978856	None	None	N
A/V	0.1119	likely_benign	0.1361	benign	-0.409	Destabilizing	0.111	N	0.451	neutral	N	0.516371566	None	None	N
A/W	0.6898	likely_pathogenic	0.7306	pathogenic	-1.197	Destabilizing	0.986	D	0.713	prob.delet.	None	None	None	None	N
A/Y	0.4072	ambiguous	0.4453	ambiguous	-0.815	Destabilizing	0.862	D	0.754	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.