TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17156	51691;51692;51693	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
N2AB	15515	46768;46769;46770	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
N2A	14588	43987;43988;43989	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
N2B	8091	24496;24497;24498	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
Novex-1	8216	24871;24872;24873	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
Novex-2	8283	25072;25073;25074	chr2:178609957;178609956;178609955	chr2:179474684;179474683;179474682
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-13
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2805
• 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
V/I	rs775371086	-0.811	0.625	N	0.569	0.132	0.416202232284	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/I	rs775371086	-0.811	0.625	N	0.569	0.132	0.416202232284	gnomAD-4.0.0	3.18801E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86315E-06	0	3.0292E-05

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
V/A	0.3769	ambiguous	0.4386	ambiguous	-1.85	Destabilizing	0.454	N	0.465	neutral	N	0.447736211	None	None	N
V/C	0.7893	likely_pathogenic	0.8306	pathogenic	-1.146	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
V/D	0.9482	likely_pathogenic	0.9347	pathogenic	-2.318	Highly Destabilizing	0.934	D	0.718	prob.delet.	N	0.511485451	None	None	N
V/E	0.9154	likely_pathogenic	0.8934	pathogenic	-2.231	Highly Destabilizing	0.842	D	0.658	neutral	None	None	None	None	N
V/F	0.485	ambiguous	0.4932	ambiguous	-1.313	Destabilizing	0.876	D	0.651	neutral	N	0.517809585	None	None	N
V/G	0.5207	ambiguous	0.5312	ambiguous	-2.267	Highly Destabilizing	0.801	D	0.701	prob.neutral	N	0.476402576	None	None	N
V/H	0.9544	likely_pathogenic	0.9518	pathogenic	-2.087	Highly Destabilizing	0.974	D	0.707	prob.neutral	None	None	None	None	N
V/I	0.1004	likely_benign	0.1038	benign	-0.743	Destabilizing	0.625	D	0.569	neutral	N	0.46697812	None	None	N
V/K	0.9367	likely_pathogenic	0.9221	pathogenic	-1.634	Destabilizing	0.842	D	0.667	neutral	None	None	None	None	N
V/L	0.4954	ambiguous	0.4821	ambiguous	-0.743	Destabilizing	0.454	N	0.477	neutral	N	0.477387115	None	None	N
V/M	0.4129	ambiguous	0.4242	ambiguous	-0.479	Destabilizing	0.991	D	0.567	neutral	None	None	None	None	N
V/N	0.8432	likely_pathogenic	0.8221	pathogenic	-1.556	Destabilizing	0.949	D	0.717	prob.delet.	None	None	None	None	N
V/P	0.8205	likely_pathogenic	0.8481	pathogenic	-1.081	Destabilizing	0.974	D	0.675	prob.neutral	None	None	None	None	N
V/Q	0.9123	likely_pathogenic	0.8891	pathogenic	-1.606	Destabilizing	0.974	D	0.678	prob.neutral	None	None	None	None	N
V/R	0.9135	likely_pathogenic	0.8889	pathogenic	-1.244	Destabilizing	0.949	D	0.711	prob.delet.	None	None	None	None	N
V/S	0.6186	likely_pathogenic	0.6447	pathogenic	-2.041	Highly Destabilizing	0.728	D	0.609	neutral	None	None	None	None	N
V/T	0.4709	ambiguous	0.4793	ambiguous	-1.841	Destabilizing	0.01	N	0.173	neutral	None	None	None	None	N
V/W	0.9486	likely_pathogenic	0.9503	pathogenic	-1.745	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
V/Y	0.8423	likely_pathogenic	0.8396	pathogenic	-1.409	Destabilizing	0.067	N	0.359	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.