TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33106	99541;99542;99543	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
N2AB	31465	94618;94619;94620	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
N2A	30538	91837;91838;91839	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
N2B	24041	72346;72347;72348	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
Novex-1	24166	72721;72722;72723	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
Novex-2	24233	72922;72923;72924	chr2:178537891;178537890;178537889	chr2:179402618;179402617;179402616
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: 6
• Structural Position: 7
• Q(SASA): 0.3591
• 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/K	None	None	0.984	N	0.564	0.377	0.355865052028	gnomAD-4.0.0	6.85091E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65815E-05

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	0.1277	likely_benign	0.127	benign	-0.552	Destabilizing	0.985	D	0.668	neutral	N	0.461196659	None	None	N
E/C	0.8755	likely_pathogenic	0.8917	pathogenic	-0.158	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.1168	likely_benign	0.1459	benign	-0.51	Destabilizing	0.013	N	0.217	neutral	N	0.469874857	None	None	N
E/F	0.78	likely_pathogenic	0.8213	pathogenic	-0.319	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/G	0.1654	likely_benign	0.1613	benign	-0.801	Destabilizing	0.997	D	0.716	prob.delet.	N	0.443651048	None	None	N
E/H	0.5623	ambiguous	0.6419	pathogenic	-0.323	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/I	0.3693	ambiguous	0.4241	ambiguous	0.088	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
E/K	0.1998	likely_benign	0.2179	benign	-0.013	Destabilizing	0.984	D	0.564	neutral	N	0.426139936	None	None	N
E/L	0.4039	ambiguous	0.4692	ambiguous	0.088	Stabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
E/M	0.4613	ambiguous	0.5178	ambiguous	0.294	Stabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	N
E/N	0.2556	likely_benign	0.2886	benign	-0.31	Destabilizing	0.984	D	0.7	prob.neutral	None	None	None	None	N
E/P	0.3387	likely_benign	0.325	benign	-0.105	Destabilizing	0.992	D	0.798	deleterious	None	None	None	None	N
E/Q	0.1675	likely_benign	0.1915	benign	-0.253	Destabilizing	0.997	D	0.631	neutral	N	0.446112563	None	None	N
E/R	0.3594	ambiguous	0.3939	ambiguous	0.205	Stabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
E/S	0.2173	likely_benign	0.2331	benign	-0.519	Destabilizing	0.977	D	0.614	neutral	None	None	None	None	N
E/T	0.2081	likely_benign	0.2378	benign	-0.32	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
E/V	0.2033	likely_benign	0.2316	benign	-0.105	Destabilizing	0.998	D	0.78	deleterious	N	0.475915395	None	None	N
E/W	0.9242	likely_pathogenic	0.9491	pathogenic	-0.133	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/Y	0.6695	likely_pathogenic	0.7365	pathogenic	-0.08	Destabilizing	1.0	D	0.769	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.