TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6555	19888;19889;19890	chr2:178728161;178728160;178728159	chr2:179592888;179592887;179592886
N2AB	6238	18937;18938;18939	chr2:178728161;178728160;178728159	chr2:179592888;179592887;179592886
N2A	5311	16156;16157;16158	chr2:178728161;178728160;178728159	chr2:179592888;179592887;179592886
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-49
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0887
• 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/L	rs753901455	None	0.015	D	0.282	0.319	0.4897983601	gnomAD-4.0.0	2.33303E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.0647E-05	0	0
V/M	rs753901455	-1.422	0.976	N	0.717	0.458	0.676562671139	gnomAD-2.1.1	2.04E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.67414E-04	None	0	0	0
V/M	rs753901455	-1.422	0.976	N	0.717	0.458	0.676562671139	gnomAD-4.0.0	1.30375E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.22009E-04	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
V/A	0.3806	ambiguous	0.4258	ambiguous	-2.282	Highly Destabilizing	0.134	N	0.355	neutral	N	0.368182136	None	None	N
V/C	0.9505	likely_pathogenic	0.9528	pathogenic	-2.18	Highly Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
V/D	0.9853	likely_pathogenic	0.9849	pathogenic	-3.159	Highly Destabilizing	0.991	D	0.845	deleterious	None	None	None	None	N
V/E	0.9716	likely_pathogenic	0.9721	pathogenic	-2.974	Highly Destabilizing	0.988	D	0.787	deleterious	N	0.521912336	None	None	N
V/F	0.5989	likely_pathogenic	0.5804	pathogenic	-1.378	Destabilizing	0.982	D	0.809	deleterious	None	None	None	None	N
V/G	0.6402	likely_pathogenic	0.6791	pathogenic	-2.78	Highly Destabilizing	0.92	D	0.783	deleterious	N	0.496971226	None	None	N
V/H	0.9927	likely_pathogenic	0.9926	pathogenic	-2.389	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/I	0.1281	likely_benign	0.12	benign	-0.896	Destabilizing	0.759	D	0.569	neutral	None	None	None	None	N
V/K	0.9869	likely_pathogenic	0.9872	pathogenic	-1.933	Destabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
V/L	0.44	ambiguous	0.4799	ambiguous	-0.896	Destabilizing	0.015	N	0.282	neutral	D	0.532102326	None	None	N
V/M	0.5158	ambiguous	0.5419	ambiguous	-1.118	Destabilizing	0.976	D	0.717	prob.delet.	N	0.510302541	None	None	N
V/N	0.9663	likely_pathogenic	0.9659	pathogenic	-2.256	Highly Destabilizing	0.997	D	0.854	deleterious	None	None	None	None	N
V/P	0.9903	likely_pathogenic	0.9904	pathogenic	-1.332	Destabilizing	0.991	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9763	likely_pathogenic	0.977	pathogenic	-2.174	Highly Destabilizing	0.997	D	0.831	deleterious	None	None	None	None	N
V/R	0.9728	likely_pathogenic	0.9735	pathogenic	-1.644	Destabilizing	0.991	D	0.847	deleterious	None	None	None	None	N
V/S	0.8175	likely_pathogenic	0.8296	pathogenic	-2.839	Highly Destabilizing	0.884	D	0.772	deleterious	None	None	None	None	N
V/T	0.7195	likely_pathogenic	0.7605	pathogenic	-2.521	Highly Destabilizing	0.939	D	0.685	prob.neutral	None	None	None	None	N
V/W	0.9929	likely_pathogenic	0.9922	pathogenic	-1.847	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/Y	0.955	likely_pathogenic	0.9484	pathogenic	-1.54	Destabilizing	0.997	D	0.814	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.