TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19509	58750;58751;58752	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
N2AB	17868	53827;53828;53829	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
N2A	16941	51046;51047;51048	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
N2B	10444	31555;31556;31557	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
Novex-1	10569	31930;31931;31932	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
Novex-2	10636	32131;32132;32133	chr2:178593775;178593774;178593773	chr2:179458502;179458501;179458500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-29
• Domain position: 31
• Structural Position: 32
• Q(SASA): 0.5549
• 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
G/S	rs1251770626	-0.345	1.0	N	0.695	0.472	0.4018988957	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/S	rs1251770626	-0.345	1.0	N	0.695	0.472	0.4018988957	gnomAD-4.0.0	1.59255E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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
G/A	0.7523	likely_pathogenic	0.8055	pathogenic	-0.109	Destabilizing	1.0	D	0.613	neutral	N	0.498526665	None	None	I
G/C	0.779	likely_pathogenic	0.8517	pathogenic	-0.834	Destabilizing	1.0	D	0.786	deleterious	D	0.526545648	None	None	I
G/D	0.9114	likely_pathogenic	0.9373	pathogenic	-0.169	Destabilizing	1.0	D	0.689	prob.neutral	D	0.52553169	None	None	I
G/E	0.9391	likely_pathogenic	0.9608	pathogenic	-0.322	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/F	0.9685	likely_pathogenic	0.9753	pathogenic	-0.86	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
G/H	0.9624	likely_pathogenic	0.9738	pathogenic	-0.255	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
G/I	0.9586	likely_pathogenic	0.9738	pathogenic	-0.339	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/K	0.9613	likely_pathogenic	0.9748	pathogenic	-0.41	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/L	0.963	likely_pathogenic	0.9705	pathogenic	-0.339	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/M	0.9704	likely_pathogenic	0.9781	pathogenic	-0.464	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
G/N	0.9025	likely_pathogenic	0.9301	pathogenic	-0.139	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
G/P	0.9964	likely_pathogenic	0.9972	pathogenic	-0.236	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/Q	0.9376	likely_pathogenic	0.9577	pathogenic	-0.37	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/R	0.9091	likely_pathogenic	0.9341	pathogenic	-0.08	Destabilizing	1.0	D	0.791	deleterious	N	0.504313563	None	None	I
G/S	0.6213	likely_pathogenic	0.6909	pathogenic	-0.324	Destabilizing	1.0	D	0.695	prob.neutral	N	0.505603783	None	None	I
G/T	0.9206	likely_pathogenic	0.9452	pathogenic	-0.402	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/V	0.9375	likely_pathogenic	0.9586	pathogenic	-0.236	Destabilizing	1.0	D	0.787	deleterious	D	0.537901953	None	None	I
G/W	0.9589	likely_pathogenic	0.9699	pathogenic	-0.982	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
G/Y	0.9556	likely_pathogenic	0.9684	pathogenic	-0.641	Destabilizing	1.0	D	0.77	deleterious	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.