TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29950	90073;90074;90075	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
N2AB	28309	85150;85151;85152	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
N2A	27382	82369;82370;82371	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
N2B	20885	62878;62879;62880	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
Novex-1	21010	63253;63254;63255	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
Novex-2	21077	63454;63455;63456	chr2:178553052;178553051;178553050	chr2:179417779;179417778;179417777
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-106
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0855
• 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/D	None	None	0.988	D	0.839	0.536	0.830956020592	gnomAD-4.0.0	1.59494E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8595E-06	0	0
V/I	None	None	0.704	N	0.547	0.201	0.466571191598	gnomAD-4.0.0	6.84901E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65722E-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	0.2914	likely_benign	0.2741	benign	-2.182	Highly Destabilizing	0.134	N	0.317	neutral	N	0.481099423	None	None	N
V/C	0.8548	likely_pathogenic	0.8512	pathogenic	-2.133	Highly Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/D	0.9914	likely_pathogenic	0.9893	pathogenic	-2.577	Highly Destabilizing	0.988	D	0.839	deleterious	D	0.543286188	None	None	N
V/E	0.9754	likely_pathogenic	0.9731	pathogenic	-2.298	Highly Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	N
V/F	0.6742	likely_pathogenic	0.6099	pathogenic	-1.291	Destabilizing	0.976	D	0.835	deleterious	N	0.517874097	None	None	N
V/G	0.7127	likely_pathogenic	0.691	pathogenic	-2.789	Highly Destabilizing	0.92	D	0.781	deleterious	D	0.54227223	None	None	N
V/H	0.9921	likely_pathogenic	0.9905	pathogenic	-2.553	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
V/I	0.0978	likely_benign	0.094	benign	-0.454	Destabilizing	0.704	D	0.547	neutral	N	0.501973341	None	None	N
V/K	0.9845	likely_pathogenic	0.9824	pathogenic	-1.722	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
V/L	0.3123	likely_benign	0.3129	benign	-0.454	Destabilizing	0.015	N	0.239	neutral	N	0.516033142	None	None	N
V/M	0.3231	likely_benign	0.2948	benign	-0.837	Destabilizing	0.982	D	0.683	prob.neutral	None	None	None	None	N
V/N	0.9636	likely_pathogenic	0.9567	pathogenic	-2.207	Highly Destabilizing	0.997	D	0.845	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9895	pathogenic	-1.004	Destabilizing	0.991	D	0.832	deleterious	None	None	None	None	N
V/Q	0.9685	likely_pathogenic	0.9642	pathogenic	-1.93	Destabilizing	0.997	D	0.827	deleterious	None	None	None	None	N
V/R	0.9747	likely_pathogenic	0.971	pathogenic	-1.754	Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
V/S	0.7775	likely_pathogenic	0.7486	pathogenic	-2.929	Highly Destabilizing	0.884	D	0.783	deleterious	None	None	None	None	N
V/T	0.5679	likely_pathogenic	0.5431	ambiguous	-2.473	Highly Destabilizing	0.939	D	0.699	prob.neutral	None	None	None	None	N
V/W	0.995	likely_pathogenic	0.9927	pathogenic	-1.734	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/Y	0.967	likely_pathogenic	0.9571	pathogenic	-1.375	Destabilizing	0.997	D	0.841	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.