TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19760	59503;59504;59505	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
N2AB	18119	54580;54581;54582	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
N2A	17192	51799;51800;51801	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
N2B	10695	32308;32309;32310	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
Novex-1	10820	32683;32684;32685	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
Novex-2	10887	32884;32885;32886	chr2:178592841;178592840;178592839	chr2:179457568;179457567;179457566
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: Fn3-31
• Domain position: 81
• Structural Position: 111
• Q(SASA): 0.1449
• 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	rs1207237676	-0.824	0.997	D	0.478	0.335	0.636040160305	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	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	0.3774	ambiguous	0.3382	benign	-2.09	Highly Destabilizing	0.999	D	0.547	neutral	N	0.489938155	None	None	N
V/C	0.704	likely_pathogenic	0.6982	pathogenic	-1.81	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/D	0.9093	likely_pathogenic	0.8912	pathogenic	-2.528	Highly Destabilizing	1.0	D	0.849	deleterious	N	0.513032841	None	None	N
V/E	0.6579	likely_pathogenic	0.6432	pathogenic	-2.384	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/F	0.3269	likely_benign	0.303	benign	-1.283	Destabilizing	1.0	D	0.798	deleterious	N	0.494813227	None	None	N
V/G	0.6261	likely_pathogenic	0.5632	ambiguous	-2.53	Highly Destabilizing	1.0	D	0.793	deleterious	D	0.527921092	None	None	N
V/H	0.8594	likely_pathogenic	0.8406	pathogenic	-1.996	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/I	0.0812	likely_benign	0.0807	benign	-0.894	Destabilizing	0.997	D	0.478	neutral	D	0.5243357	None	None	N
V/K	0.6507	likely_pathogenic	0.6255	pathogenic	-1.574	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/L	0.36	ambiguous	0.3382	benign	-0.894	Destabilizing	0.997	D	0.525	neutral	N	0.479516448	None	None	N
V/M	0.2084	likely_benign	0.1883	benign	-1.08	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
V/N	0.7819	likely_pathogenic	0.7517	pathogenic	-1.744	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/P	0.9909	likely_pathogenic	0.9873	pathogenic	-1.266	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/Q	0.5805	likely_pathogenic	0.5682	pathogenic	-1.743	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/R	0.6134	likely_pathogenic	0.5836	pathogenic	-1.259	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/S	0.5613	ambiguous	0.5197	ambiguous	-2.356	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/T	0.3793	ambiguous	0.3481	ambiguous	-2.089	Highly Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
V/W	0.9216	likely_pathogenic	0.9062	pathogenic	-1.614	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/Y	0.77	likely_pathogenic	0.7542	pathogenic	-1.311	Destabilizing	1.0	D	0.807	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.