TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25771	77536;77537;77538	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
N2AB	24130	72613;72614;72615	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
N2A	23203	69832;69833;69834	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
N2B	16706	50341;50342;50343	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
Novex-1	16831	50716;50717;50718	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
Novex-2	16898	50917;50918;50919	chr2:178568821;178568820;178568819	chr2:179433548;179433547;179433546
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-75
• Domain position: 74
• Structural Position: 108
• Q(SASA): 0.0839
• 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/A	None	None	1.0	D	0.639	0.795	0.809015641971	gnomAD-4.0.0	6.84433E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99599E-07	0	0
V/G	rs1184590631	-3.718	1.0	D	0.88	0.841	0.952205082084	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
V/G	rs1184590631	-3.718	1.0	D	0.88	0.841	0.952205082084	gnomAD-4.0.0	6.84433E-07	None	None	None	None	N	None	0	0	None	0	2.52372E-05	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
V/A	0.9127	likely_pathogenic	0.9004	pathogenic	-2.681	Highly Destabilizing	1.0	D	0.639	neutral	D	0.566633677	None	None	N
V/C	0.985	likely_pathogenic	0.9846	pathogenic	-2.109	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9993	pathogenic	-3.565	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.644342203	None	None	N
V/E	0.9973	likely_pathogenic	0.9975	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/F	0.9702	likely_pathogenic	0.9682	pathogenic	-1.505	Destabilizing	1.0	D	0.794	deleterious	D	0.578154567	None	None	N
V/G	0.9704	likely_pathogenic	0.9724	pathogenic	-3.222	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.644342203	None	None	N
V/H	0.9994	likely_pathogenic	0.9995	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/I	0.134	likely_benign	0.1111	benign	-1.089	Destabilizing	0.998	D	0.596	neutral	D	0.525040281	None	None	N
V/K	0.9983	likely_pathogenic	0.9985	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/L	0.8451	likely_pathogenic	0.8277	pathogenic	-1.089	Destabilizing	0.995	D	0.648	neutral	N	0.516988039	None	None	N
V/M	0.8989	likely_pathogenic	0.8801	pathogenic	-1.358	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/N	0.9973	likely_pathogenic	0.9972	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/P	0.9979	likely_pathogenic	0.9976	pathogenic	-1.606	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Q	0.9977	likely_pathogenic	0.9978	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9967	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
V/S	0.9871	likely_pathogenic	0.9863	pathogenic	-3.354	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/T	0.9426	likely_pathogenic	0.9391	pathogenic	-2.93	Highly Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9997	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9977	likely_pathogenic	0.9977	pathogenic	-1.834	Destabilizing	1.0	D	0.805	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.