TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15501	46726;46727;46728	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
N2AB	13860	41803;41804;41805	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
N2A	12933	39022;39023;39024	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
N2B	6436	19531;19532;19533	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
Novex-1	6561	19906;19907;19908	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
Novex-2	6628	20107;20108;20109	chr2:178619816;178619815;178619814	chr2:179484543;179484542;179484541
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-107
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0796
• 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
A/T	None	None	0.992	D	0.669	0.585	0.594113984522	gnomAD-4.0.0	1.59457E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86454E-06	0	0
A/V	None	None	0.619	N	0.413	0.392	0.526995340713	gnomAD-4.0.0	1.59458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86456E-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
A/C	0.4933	ambiguous	0.5709	pathogenic	-0.916	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
A/D	0.9966	likely_pathogenic	0.9954	pathogenic	-2.658	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
A/E	0.9921	likely_pathogenic	0.9885	pathogenic	-2.358	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.547365735	None	None	N
A/F	0.9645	likely_pathogenic	0.9576	pathogenic	-0.574	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
A/G	0.4091	ambiguous	0.4237	ambiguous	-1.65	Destabilizing	0.999	D	0.635	neutral	D	0.525290617	None	None	N
A/H	0.9951	likely_pathogenic	0.9928	pathogenic	-2.269	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
A/I	0.7161	likely_pathogenic	0.7841	pathogenic	0.421	Stabilizing	0.988	D	0.742	deleterious	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9976	pathogenic	-1.07	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/L	0.664	likely_pathogenic	0.7145	pathogenic	0.421	Stabilizing	0.988	D	0.707	prob.neutral	None	None	None	None	N
A/M	0.7985	likely_pathogenic	0.8229	pathogenic	-0.005	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/N	0.9863	likely_pathogenic	0.9837	pathogenic	-1.701	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/P	0.9893	likely_pathogenic	0.988	pathogenic	-0.052	Destabilizing	1.0	D	0.843	deleterious	D	0.547365735	None	None	N
A/Q	0.9847	likely_pathogenic	0.9798	pathogenic	-1.301	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/R	0.993	likely_pathogenic	0.9905	pathogenic	-1.475	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/S	0.4072	ambiguous	0.3699	ambiguous	-2.005	Highly Destabilizing	0.996	D	0.651	neutral	D	0.547806922	None	None	N
A/T	0.4405	ambiguous	0.4142	ambiguous	-1.566	Destabilizing	0.992	D	0.669	neutral	D	0.54828533	None	None	N
A/V	0.3037	likely_benign	0.3405	ambiguous	-0.052	Destabilizing	0.619	D	0.413	neutral	N	0.475870635	None	None	N
A/W	0.9974	likely_pathogenic	0.9966	pathogenic	-1.474	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
A/Y	0.9898	likely_pathogenic	0.985	pathogenic	-0.912	Destabilizing	1.0	D	0.903	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.