TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22572	67939;67940;67941	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
N2AB	20931	63016;63017;63018	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
N2A	20004	60235;60236;60237	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
N2B	13507	40744;40745;40746	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
Novex-1	13632	41119;41120;41121	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
Novex-2	13699	41320;41321;41322	chr2:178579316;178579315;178579314	chr2:179444043;179444042;179444041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-127
• Domain position: 13
• Structural Position: 33
• Q(SASA): 0.2934
• 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
I/F	rs779301386	-1.444	0.217	N	0.471	0.26	0.355658859761	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/F	rs779301386	-1.444	0.217	N	0.471	0.26	0.355658859761	gnomAD-4.0.0	1.60123E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87743E-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
I/A	0.969	likely_pathogenic	0.9636	pathogenic	-1.809	Destabilizing	0.996	D	0.62	neutral	None	None	None	None	I
I/C	0.9569	likely_pathogenic	0.953	pathogenic	-1.201	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
I/D	0.9976	likely_pathogenic	0.9973	pathogenic	-1.248	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
I/E	0.9961	likely_pathogenic	0.995	pathogenic	-1.186	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	I
I/F	0.4106	ambiguous	0.408	ambiguous	-1.152	Destabilizing	0.217	N	0.471	neutral	N	0.460389375	None	None	I
I/G	0.9924	likely_pathogenic	0.9905	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
I/H	0.9869	likely_pathogenic	0.9843	pathogenic	-1.239	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/K	0.9905	likely_pathogenic	0.9874	pathogenic	-1.312	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
I/L	0.2324	likely_benign	0.2124	benign	-0.822	Destabilizing	0.889	D	0.548	neutral	N	0.452792052	None	None	I
I/M	0.3485	ambiguous	0.3497	ambiguous	-0.723	Destabilizing	0.999	D	0.639	neutral	N	0.510947036	None	None	I
I/N	0.9655	likely_pathogenic	0.959	pathogenic	-1.277	Destabilizing	0.999	D	0.817	deleterious	N	0.483773549	None	None	I
I/P	0.9949	likely_pathogenic	0.9936	pathogenic	-1.121	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
I/Q	0.9908	likely_pathogenic	0.9886	pathogenic	-1.358	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
I/R	0.9872	likely_pathogenic	0.984	pathogenic	-0.749	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
I/S	0.9727	likely_pathogenic	0.9686	pathogenic	-1.932	Destabilizing	0.999	D	0.743	deleterious	N	0.471910265	None	None	I
I/T	0.9763	likely_pathogenic	0.9703	pathogenic	-1.734	Destabilizing	0.999	D	0.688	prob.neutral	N	0.459882396	None	None	I
I/V	0.2058	likely_benign	0.191	benign	-1.121	Destabilizing	0.941	D	0.533	neutral	N	0.44643141	None	None	I
I/W	0.9752	likely_pathogenic	0.9729	pathogenic	-1.239	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/Y	0.8918	likely_pathogenic	0.884	pathogenic	-1.021	Destabilizing	0.995	D	0.681	prob.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.