TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22347	67264;67265;67266	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
N2AB	20706	62341;62342;62343	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
N2A	19779	59560;59561;59562	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
N2B	13282	40069;40070;40071	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
Novex-1	13407	40444;40445;40446	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
Novex-2	13474	40645;40646;40647	chr2:178580340;178580339;178580338	chr2:179445067;179445066;179445065
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-126
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.1727
• 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
I/T	None	None	0.008	N	0.501	0.307	0.712308658724	gnomAD-4.0.0	9.60368E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05012E-05	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	0.7698	likely_pathogenic	0.7537	pathogenic	-2.568	Highly Destabilizing	0.415	N	0.675	prob.neutral	None	None	None	None	N
I/C	0.922	likely_pathogenic	0.9014	pathogenic	-2.092	Highly Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
I/D	0.9989	likely_pathogenic	0.9987	pathogenic	-2.234	Highly Destabilizing	0.923	D	0.827	deleterious	None	None	None	None	N
I/E	0.9961	likely_pathogenic	0.9953	pathogenic	-1.982	Destabilizing	0.923	D	0.822	deleterious	None	None	None	None	N
I/F	0.5827	likely_pathogenic	0.4775	ambiguous	-1.426	Destabilizing	0.901	D	0.693	prob.neutral	D	0.526517574	None	None	N
I/G	0.9871	likely_pathogenic	0.9841	pathogenic	-3.157	Highly Destabilizing	0.923	D	0.816	deleterious	None	None	None	None	N
I/H	0.9948	likely_pathogenic	0.9926	pathogenic	-2.461	Highly Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
I/K	0.9926	likely_pathogenic	0.991	pathogenic	-1.995	Destabilizing	0.923	D	0.819	deleterious	None	None	None	None	N
I/L	0.297	likely_benign	0.2522	benign	-0.864	Destabilizing	0.19	N	0.5	neutral	N	0.473643094	None	None	N
I/M	0.2916	likely_benign	0.217	benign	-0.963	Destabilizing	0.949	D	0.679	prob.neutral	N	0.52041049	None	None	N
I/N	0.9811	likely_pathogenic	0.9776	pathogenic	-2.329	Highly Destabilizing	0.901	D	0.828	deleterious	N	0.520917469	None	None	N
I/P	0.9941	likely_pathogenic	0.9939	pathogenic	-1.412	Destabilizing	0.961	D	0.827	deleterious	None	None	None	None	N
I/Q	0.9919	likely_pathogenic	0.9894	pathogenic	-2.117	Highly Destabilizing	0.961	D	0.834	deleterious	None	None	None	None	N
I/R	0.9868	likely_pathogenic	0.9851	pathogenic	-1.814	Destabilizing	0.923	D	0.829	deleterious	None	None	None	None	N
I/S	0.9465	likely_pathogenic	0.9403	pathogenic	-3.179	Highly Destabilizing	0.565	D	0.77	deleterious	N	0.490442951	None	None	N
I/T	0.8117	likely_pathogenic	0.7986	pathogenic	-2.754	Highly Destabilizing	0.008	N	0.501	neutral	N	0.501292277	None	None	N
I/V	0.0863	likely_benign	0.082	benign	-1.412	Destabilizing	0.003	N	0.212	neutral	N	0.456577486	None	None	N
I/W	0.9933	likely_pathogenic	0.9903	pathogenic	-1.671	Destabilizing	0.996	D	0.797	deleterious	None	None	None	None	N
I/Y	0.963	likely_pathogenic	0.9502	pathogenic	-1.432	Destabilizing	0.961	D	0.767	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.