TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26042	78349;78350;78351	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
N2AB	24401	73426;73427;73428	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
N2A	23474	70645;70646;70647	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
N2B	16977	51154;51155;51156	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
Novex-1	17102	51529;51530;51531	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
Novex-2	17169	51730;51731;51732	chr2:178568008;178568007;178568006	chr2:179432735;179432734;179432733
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-77
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.8992
• 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
K/T	rs1261267302	-0.023	1.0	N	0.688	0.582	0.400033932507	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/T	rs1261267302	-0.023	1.0	N	0.688	0.582	0.400033932507	gnomAD-4.0.0	5.4749E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19687E-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
K/A	0.6777	likely_pathogenic	0.7435	pathogenic	0.012	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/C	0.8989	likely_pathogenic	0.9152	pathogenic	-0.4	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.7512	likely_pathogenic	0.7948	pathogenic	-0.23	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/E	0.5079	ambiguous	0.5844	pathogenic	-0.25	Destabilizing	0.999	D	0.67	neutral	N	0.504818858	None	None	N
K/F	0.9617	likely_pathogenic	0.9717	pathogenic	-0.355	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
K/G	0.6846	likely_pathogenic	0.7381	pathogenic	-0.104	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
K/H	0.5019	ambiguous	0.5395	ambiguous	-0.224	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/I	0.8169	likely_pathogenic	0.8653	pathogenic	0.232	Stabilizing	1.0	D	0.699	prob.neutral	N	0.468300457	None	None	N
K/L	0.7592	likely_pathogenic	0.8125	pathogenic	0.232	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
K/M	0.6489	likely_pathogenic	0.7135	pathogenic	-0.057	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/N	0.6424	likely_pathogenic	0.7168	pathogenic	0.067	Stabilizing	1.0	D	0.758	deleterious	N	0.468277685	None	None	N
K/P	0.8118	likely_pathogenic	0.8509	pathogenic	0.182	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/Q	0.2785	likely_benign	0.3272	benign	-0.087	Destabilizing	1.0	D	0.756	deleterious	N	0.474647241	None	None	N
K/R	0.0922	likely_benign	0.0946	benign	-0.085	Destabilizing	0.999	D	0.631	neutral	N	0.464897097	None	None	N
K/S	0.6574	likely_pathogenic	0.731	pathogenic	-0.309	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
K/T	0.4156	ambiguous	0.5031	ambiguous	-0.216	Destabilizing	1.0	D	0.688	prob.neutral	N	0.48579038	None	None	N
K/V	0.7546	likely_pathogenic	0.8092	pathogenic	0.182	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/W	0.932	likely_pathogenic	0.9438	pathogenic	-0.455	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Y	0.8751	likely_pathogenic	0.895	pathogenic	-0.099	Destabilizing	1.0	D	0.666	neutral	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.