TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31993	96202;96203;96204	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
N2AB	30352	91279;91280;91281	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
N2A	29425	88498;88499;88500	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
N2B	22928	69007;69008;69009	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
Novex-1	23053	69382;69383;69384	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
Novex-2	23120	69583;69584;69585	chr2:178544252;178544251;178544250	chr2:179408979;179408978;179408977
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-121
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.4939
• Predicted PPI site: I

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
M/I	rs749913152	0.119	None	N	0.193	0.08	0.356897458496	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
M/I	rs749913152	0.119	None	N	0.193	0.08	0.356897458496	gnomAD-4.0.0	6.84229E-07	None	None	None	None	I	None	2.98811E-05	0	None	0	0	None	0	0	0	0	0
M/L	None	None	0.003	N	0.181	0.121	0.459995458672	gnomAD-4.0.0	3.1827E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71719E-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
M/A	0.2815	likely_benign	0.2949	benign	-0.838	Destabilizing	0.025	N	0.336	neutral	None	None	None	None	I
M/C	0.5928	likely_pathogenic	0.5872	pathogenic	-0.772	Destabilizing	0.859	D	0.538	neutral	None	None	None	None	I
M/D	0.7149	likely_pathogenic	0.693	pathogenic	0.491	Stabilizing	0.22	N	0.567	neutral	None	None	None	None	I
M/E	0.3551	ambiguous	0.3464	ambiguous	0.488	Stabilizing	0.055	N	0.505	neutral	None	None	None	None	I
M/F	0.2266	likely_benign	0.2299	benign	-0.114	Destabilizing	0.22	N	0.439	neutral	None	None	None	None	I
M/G	0.5104	ambiguous	0.4988	ambiguous	-1.092	Destabilizing	0.104	N	0.511	neutral	None	None	None	None	I
M/H	0.4294	ambiguous	0.4292	ambiguous	-0.111	Destabilizing	0.667	D	0.588	neutral	None	None	None	None	I
M/I	0.2123	likely_benign	0.2076	benign	-0.233	Destabilizing	None	N	0.193	neutral	N	0.412905988	None	None	I
M/K	0.1591	likely_benign	0.1467	benign	0.257	Stabilizing	None	N	0.279	neutral	N	0.436148207	None	None	I
M/L	0.1005	likely_benign	0.1015	benign	-0.233	Destabilizing	0.003	N	0.181	neutral	N	0.404670507	None	None	I
M/N	0.3567	ambiguous	0.3556	ambiguous	0.342	Stabilizing	0.22	N	0.565	neutral	None	None	None	None	I
M/P	0.4076	ambiguous	0.4277	ambiguous	-0.405	Destabilizing	0.364	N	0.561	neutral	None	None	None	None	I
M/Q	0.2016	likely_benign	0.1989	benign	0.262	Stabilizing	0.22	N	0.422	neutral	None	None	None	None	I
M/R	0.1745	likely_benign	0.1602	benign	0.689	Stabilizing	0.096	N	0.457	neutral	N	0.44476769	None	None	I
M/S	0.3241	likely_benign	0.3315	benign	-0.268	Destabilizing	0.055	N	0.44	neutral	None	None	None	None	I
M/T	0.1585	likely_benign	0.1654	benign	-0.151	Destabilizing	None	N	0.273	neutral	N	0.440111232	None	None	I
M/V	0.0851	likely_benign	0.0831	benign	-0.405	Destabilizing	None	N	0.194	neutral	N	0.422178832	None	None	I
M/W	0.5435	ambiguous	0.5226	ambiguous	-0.063	Destabilizing	0.958	D	0.531	neutral	None	None	None	None	I
M/Y	0.4355	ambiguous	0.4283	ambiguous	0.023	Stabilizing	0.364	N	0.574	neutral	None	None	None	None	I

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.