TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32563	97912;97913;97914	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
N2AB	30922	92989;92990;92991	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
N2A	29995	90208;90209;90210	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
N2B	23498	70717;70718;70719	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
Novex-1	23623	71092;71093;71094	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
Novex-2	23690	71293;71294;71295	chr2:178541390;178541389;178541388	chr2:179406117;179406116;179406115
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: Fn3-125
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.4109
• 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
G/D	rs1268910714	0.119	1.0	N	0.742	0.436	0.310458034454	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
G/D	rs1268910714	0.119	1.0	N	0.742	0.436	0.310458034454	gnomAD-4.0.0	1.59747E-06	None	None	None	None	N	None	0	2.29716E-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
G/A	0.2345	likely_benign	0.2483	benign	-0.212	Destabilizing	1.0	D	0.693	prob.neutral	N	0.504934403	None	None	N
G/C	0.3404	ambiguous	0.3569	ambiguous	-0.821	Destabilizing	1.0	D	0.716	prob.delet.	N	0.521343591	None	None	N
G/D	0.3456	ambiguous	0.3824	ambiguous	-0.058	Destabilizing	1.0	D	0.742	deleterious	N	0.499431681	None	None	N
G/E	0.427	ambiguous	0.4673	ambiguous	-0.213	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
G/F	0.7282	likely_pathogenic	0.759	pathogenic	-0.927	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/H	0.553	ambiguous	0.5738	pathogenic	-0.435	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
G/I	0.638	likely_pathogenic	0.6792	pathogenic	-0.354	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/K	0.6952	likely_pathogenic	0.7153	pathogenic	-0.516	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
G/L	0.6151	likely_pathogenic	0.6361	pathogenic	-0.354	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
G/M	0.6244	likely_pathogenic	0.6489	pathogenic	-0.42	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/N	0.3168	likely_benign	0.3185	benign	-0.214	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/P	0.9444	likely_pathogenic	0.9578	pathogenic	-0.274	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/Q	0.4961	ambiguous	0.5176	ambiguous	-0.454	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
G/R	0.5442	ambiguous	0.5804	pathogenic	-0.181	Destabilizing	1.0	D	0.748	deleterious	N	0.47282727	None	None	N
G/S	0.1458	likely_benign	0.1579	benign	-0.43	Destabilizing	1.0	D	0.761	deleterious	N	0.472066801	None	None	N
G/T	0.3206	likely_benign	0.3485	ambiguous	-0.503	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
G/V	0.4904	ambiguous	0.5479	ambiguous	-0.274	Destabilizing	1.0	D	0.742	deleterious	N	0.521090101	None	None	N
G/W	0.6406	likely_pathogenic	0.6998	pathogenic	-1.072	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
G/Y	0.6264	likely_pathogenic	0.6522	pathogenic	-0.705	Destabilizing	1.0	D	0.733	prob.delet.	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.