TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33164	99715;99716;99717	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
N2AB	31523	94792;94793;94794	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
N2A	30596	92011;92012;92013	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
N2B	24099	72520;72521;72522	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
Novex-1	24224	72895;72896;72897	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
Novex-2	24291	73096;73097;73098	chr2:178537717;178537716;178537715	chr2:179402444;179402443;179402442
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-156
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2275
• 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
E/Q	rs753191182	-0.213	1.0	N	0.645	0.274	0.390220360785	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	1.56E-05	0
E/Q	rs753191182	-0.213	1.0	N	0.645	0.274	0.390220360785	gnomAD-4.0.0	6.84223E-07	None	None	None	None	N	None	0	2.23694E-05	None	0	0	None	0	0	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
E/A	0.2493	likely_benign	0.3312	benign	-0.525	Destabilizing	0.998	D	0.612	neutral	N	0.429625745	None	None	N
E/C	0.9309	likely_pathogenic	0.9414	pathogenic	-0.037	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/D	0.2284	likely_benign	0.2901	benign	-0.463	Destabilizing	0.988	D	0.437	neutral	N	0.447576788	None	None	N
E/F	0.8709	likely_pathogenic	0.9003	pathogenic	-0.417	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/G	0.2675	likely_benign	0.3095	benign	-0.744	Destabilizing	1.0	D	0.652	neutral	N	0.462007522	None	None	N
E/H	0.7462	likely_pathogenic	0.7705	pathogenic	-0.345	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/I	0.6127	likely_pathogenic	0.7165	pathogenic	0.028	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.3524	ambiguous	0.4073	ambiguous	0.177	Stabilizing	0.999	D	0.586	neutral	N	0.4181766	None	None	N
E/L	0.5976	likely_pathogenic	0.6621	pathogenic	0.028	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/M	0.5875	likely_pathogenic	0.6772	pathogenic	0.279	Stabilizing	0.999	D	0.661	neutral	None	None	None	None	N
E/N	0.4141	ambiguous	0.4817	ambiguous	-0.135	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/P	0.9811	likely_pathogenic	0.9765	pathogenic	-0.136	Destabilizing	0.997	D	0.671	neutral	None	None	None	None	N
E/Q	0.2229	likely_benign	0.2554	benign	-0.102	Destabilizing	1.0	D	0.645	neutral	N	0.38269859	None	None	N
E/R	0.5321	ambiguous	0.5503	ambiguous	0.347	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/S	0.3696	ambiguous	0.4399	ambiguous	-0.319	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/T	0.3767	ambiguous	0.4797	ambiguous	-0.141	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/V	0.3901	ambiguous	0.4947	ambiguous	-0.136	Destabilizing	0.999	D	0.701	prob.neutral	N	0.451849244	None	None	N
E/W	0.9725	likely_pathogenic	0.9759	pathogenic	-0.255	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/Y	0.8085	likely_pathogenic	0.8308	pathogenic	-0.175	Destabilizing	1.0	D	0.688	prob.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.