TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3147	9664;9665;9666	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
N2AB	3147	9664;9665;9666	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
N2A	3147	9664;9665;9666	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
N2B	3101	9526;9527;9528	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
Novex-1	3101	9526;9527;9528	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
Novex-2	3101	9526;9527;9528	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516
Novex-3	3147	9664;9665;9666	chr2:178767791;178767790;178767789	chr2:179632518;179632517;179632516

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-22
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.824
• 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	rs150283731	-0.099	0.02	N	0.213	0.073	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	0	None	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
V/A	0.919	likely_pathogenic	0.8911	pathogenic	-1.364	Destabilizing	0.863	D	0.483	neutral	N	0.315322813	None	None	N
V/C	0.9819	likely_pathogenic	0.9769	pathogenic	-0.889	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
V/D	0.99	likely_pathogenic	0.989	pathogenic	-1.13	Destabilizing	0.997	D	0.674	neutral	N	0.318447777	None	None	N
V/E	0.9718	likely_pathogenic	0.9699	pathogenic	-1.162	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	N
V/F	0.851	likely_pathogenic	0.8627	pathogenic	-1.166	Destabilizing	0.982	D	0.516	neutral	N	0.317257418	None	None	N
V/G	0.943	likely_pathogenic	0.9282	pathogenic	-1.654	Destabilizing	0.997	D	0.677	prob.neutral	N	0.317993073	None	None	N
V/H	0.9943	likely_pathogenic	0.9936	pathogenic	-1.226	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
V/I	0.1016	likely_benign	0.1236	benign	-0.684	Destabilizing	0.02	N	0.213	neutral	N	0.353063661	None	None	N
V/K	0.9788	likely_pathogenic	0.9784	pathogenic	-1.156	Destabilizing	0.993	D	0.628	neutral	None	None	None	None	N
V/L	0.7595	likely_pathogenic	0.7799	pathogenic	-0.684	Destabilizing	0.76	D	0.361	neutral	N	0.314622626	None	None	N
V/M	0.6979	likely_pathogenic	0.7414	pathogenic	-0.468	Destabilizing	0.986	D	0.473	neutral	None	None	None	None	N
V/N	0.9716	likely_pathogenic	0.9696	pathogenic	-0.861	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
V/P	0.9876	likely_pathogenic	0.9639	pathogenic	-0.875	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
V/Q	0.9761	likely_pathogenic	0.9756	pathogenic	-1.063	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
V/R	0.9706	likely_pathogenic	0.9674	pathogenic	-0.613	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
V/S	0.9529	likely_pathogenic	0.9439	pathogenic	-1.354	Destabilizing	0.993	D	0.595	neutral	None	None	None	None	N
V/T	0.8385	likely_pathogenic	0.8305	pathogenic	-1.277	Destabilizing	0.953	D	0.44	neutral	None	None	None	None	N
V/W	0.9963	likely_pathogenic	0.996	pathogenic	-1.323	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
V/Y	0.9836	likely_pathogenic	0.9829	pathogenic	-1.043	Destabilizing	0.998	D	0.499	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.