TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29806	89641;89642;89643	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
N2AB	28165	84718;84719;84720	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
N2A	27238	81937;81938;81939	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
N2B	20741	62446;62447;62448	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
Novex-1	20866	62821;62822;62823	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
Novex-2	20933	63022;63023;63024	chr2:178553589;178553588;178553587	chr2:179418316;179418315;179418314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-105
• Domain position: 73
• Structural Position: 104
• Q(SASA): 0.0849
• 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
Y/D	rs982322225	-3.489	1.0	D	0.883	0.928	0.941281488252	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
Y/D	rs982322225	-3.489	1.0	D	0.883	0.928	0.941281488252	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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
Y/A	0.9567	likely_pathogenic	0.9573	pathogenic	-2.795	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/C	0.5758	likely_pathogenic	0.5991	pathogenic	-1.573	Destabilizing	1.0	D	0.872	deleterious	D	0.625574306	None	None	N
Y/D	0.9621	likely_pathogenic	0.96	pathogenic	-3.563	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.667131778	None	None	N
Y/E	0.9914	likely_pathogenic	0.9922	pathogenic	-3.339	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/F	0.2944	likely_benign	0.2979	benign	-1.007	Destabilizing	0.999	D	0.756	deleterious	D	0.597059132	None	None	N
Y/G	0.9135	likely_pathogenic	0.9123	pathogenic	-3.217	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/H	0.8224	likely_pathogenic	0.8388	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.667131778	None	None	N
Y/I	0.9016	likely_pathogenic	0.9144	pathogenic	-1.386	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/K	0.9908	likely_pathogenic	0.9914	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/L	0.8597	likely_pathogenic	0.8698	pathogenic	-1.386	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
Y/M	0.9524	likely_pathogenic	0.9585	pathogenic	-1.137	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.7806	likely_pathogenic	0.7887	pathogenic	-3.167	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.666929974	None	None	N
Y/P	0.9954	likely_pathogenic	0.9947	pathogenic	-1.872	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/Q	0.9803	likely_pathogenic	0.9827	pathogenic	-2.84	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/R	0.9634	likely_pathogenic	0.9664	pathogenic	-2.189	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.8387	likely_pathogenic	0.8443	pathogenic	-3.413	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.667131778	None	None	N
Y/T	0.9259	likely_pathogenic	0.9343	pathogenic	-3.061	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/V	0.8247	likely_pathogenic	0.8452	pathogenic	-1.872	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/W	0.7992	likely_pathogenic	0.8197	pathogenic	-0.362	Destabilizing	1.0	D	0.811	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.