TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6586	19981;19982;19983	chr2:178727822;178727821;178727820	chr2:179592549;179592548;179592547
N2AB	6269	19030;19031;19032	chr2:178727822;178727821;178727820	chr2:179592549;179592548;179592547
N2A	5342	16249;16250;16251	chr2:178727822;178727821;178727820	chr2:179592549;179592548;179592547
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: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-50
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.4223
• 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/T	rs896710187	None	0.324	N	0.359	0.136	0.642625386947	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
I/T	rs896710187	None	0.324	N	0.359	0.136	0.642625386947	gnomAD-4.0.0	6.21717E-06	None	None	None	None	N	None	1.33837E-05	0	None	0	0	None	0	0	7.64588E-06	0	0
I/V	None	None	None	N	0.173	0.085	0.42573502686	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	0.2884	likely_benign	0.2034	benign	-0.559	Destabilizing	0.116	N	0.369	neutral	None	None	None	None	N
I/C	0.7392	likely_pathogenic	0.6448	pathogenic	-0.613	Destabilizing	0.944	D	0.361	neutral	None	None	None	None	N
I/D	0.5456	ambiguous	0.4043	ambiguous	-0.041	Destabilizing	0.818	D	0.496	neutral	None	None	None	None	N
I/E	0.4681	ambiguous	0.3684	ambiguous	-0.129	Destabilizing	0.818	D	0.495	neutral	None	None	None	None	N
I/F	0.1559	likely_benign	0.1198	benign	-0.555	Destabilizing	0.69	D	0.334	neutral	None	None	None	None	N
I/G	0.5648	likely_pathogenic	0.4156	ambiguous	-0.725	Destabilizing	0.818	D	0.479	neutral	None	None	None	None	N
I/H	0.4597	ambiguous	0.3404	ambiguous	-0.03	Destabilizing	0.981	D	0.481	neutral	None	None	None	None	N
I/K	0.312	likely_benign	0.227	benign	-0.293	Destabilizing	0.773	D	0.489	neutral	N	0.500501622	None	None	N
I/L	0.0967	likely_benign	0.0814	benign	-0.246	Destabilizing	0.001	N	0.163	neutral	N	0.390912641	None	None	N
I/M	0.1102	likely_benign	0.0916	benign	-0.339	Destabilizing	0.627	D	0.359	neutral	N	0.499984334	None	None	N
I/N	0.2174	likely_benign	0.1324	benign	-0.111	Destabilizing	0.932	D	0.49	neutral	None	None	None	None	N
I/P	0.5843	likely_pathogenic	0.4788	ambiguous	-0.317	Destabilizing	0.932	D	0.494	neutral	None	None	None	None	N
I/Q	0.374	ambiguous	0.2758	benign	-0.318	Destabilizing	0.932	D	0.487	neutral	None	None	None	None	N
I/R	0.2675	likely_benign	0.1916	benign	0.229	Stabilizing	0.773	D	0.491	neutral	N	0.492306213	None	None	N
I/S	0.2432	likely_benign	0.1635	benign	-0.579	Destabilizing	0.69	D	0.472	neutral	None	None	None	None	N
I/T	0.244	likely_benign	0.1637	benign	-0.556	Destabilizing	0.324	N	0.359	neutral	N	0.481435858	None	None	N
I/V	0.076	likely_benign	0.0646	benign	-0.317	Destabilizing	None	N	0.173	neutral	N	0.455366765	None	None	N
I/W	0.7552	likely_pathogenic	0.6937	pathogenic	-0.582	Destabilizing	0.981	D	0.557	neutral	None	None	None	None	N
I/Y	0.4714	ambiguous	0.395	ambiguous	-0.323	Destabilizing	0.818	D	0.385	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.