TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32060	96403;96404;96405	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
N2AB	30419	91480;91481;91482	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
N2A	29492	88699;88700;88701	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
N2B	22995	69208;69209;69210	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
Novex-1	23120	69583;69584;69585	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
Novex-2	23187	69784;69785;69786	chr2:178543966;178543965;178543964	chr2:179408693;179408692;179408691
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-153
• Domain position: 44
• Structural Position: 122
• Q(SASA): 0.3406
• 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/S	None	None	0.784	N	0.397	0.248	0.698813973971	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	0.3206	likely_benign	0.2765	benign	-0.99	Destabilizing	0.495	N	0.353	neutral	None	None	None	None	N
I/C	0.6589	likely_pathogenic	0.6018	pathogenic	-0.809	Destabilizing	0.995	D	0.404	neutral	None	None	None	None	N
I/D	0.6859	likely_pathogenic	0.6207	pathogenic	-0.364	Destabilizing	0.981	D	0.473	neutral	None	None	None	None	N
I/E	0.5947	likely_pathogenic	0.5377	ambiguous	-0.392	Destabilizing	0.944	D	0.476	neutral	None	None	None	None	N
I/F	0.1415	likely_benign	0.1265	benign	-0.642	Destabilizing	0.006	N	0.177	neutral	N	0.486689749	None	None	N
I/G	0.6153	likely_pathogenic	0.543	ambiguous	-1.244	Destabilizing	0.828	D	0.434	neutral	None	None	None	None	N
I/H	0.4523	ambiguous	0.3962	ambiguous	-0.387	Destabilizing	0.893	D	0.455	neutral	None	None	None	None	N
I/K	0.4455	ambiguous	0.3818	ambiguous	-0.69	Destabilizing	0.828	D	0.463	neutral	None	None	None	None	N
I/L	0.1097	likely_benign	0.1013	benign	-0.401	Destabilizing	0.002	N	0.127	neutral	N	0.46437025	None	None	N
I/M	0.0902	likely_benign	0.0829	benign	-0.501	Destabilizing	0.139	N	0.217	neutral	N	0.507353023	None	None	N
I/N	0.2548	likely_benign	0.2088	benign	-0.572	Destabilizing	0.975	D	0.472	neutral	N	0.449862157	None	None	N
I/P	0.9323	likely_pathogenic	0.8948	pathogenic	-0.564	Destabilizing	0.981	D	0.473	neutral	None	None	None	None	N
I/Q	0.4087	ambiguous	0.3619	ambiguous	-0.718	Destabilizing	0.944	D	0.465	neutral	None	None	None	None	N
I/R	0.3544	ambiguous	0.2881	benign	-0.146	Destabilizing	0.944	D	0.468	neutral	None	None	None	None	N
I/S	0.2813	likely_benign	0.2389	benign	-1.113	Destabilizing	0.784	D	0.397	neutral	N	0.441608034	None	None	N
I/T	0.283	likely_benign	0.2431	benign	-1.021	Destabilizing	0.642	D	0.355	neutral	N	0.465004968	None	None	N
I/V	0.0728	likely_benign	0.0676	benign	-0.564	Destabilizing	0.139	N	0.244	neutral	N	0.457097561	None	None	N
I/W	0.7249	likely_pathogenic	0.6598	pathogenic	-0.686	Destabilizing	0.995	D	0.435	neutral	None	None	None	None	N
I/Y	0.432	ambiguous	0.3771	ambiguous	-0.456	Destabilizing	0.013	N	0.171	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.