TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8089	24490;24491;24492	chr2:178718935;178718934;178718933	chr2:179583662;179583661;179583660
N2AB	7772	23539;23540;23541	chr2:178718935;178718934;178718933	chr2:179583662;179583661;179583660
N2A	6845	20758;20759;20760	chr2:178718935;178718934;178718933	chr2:179583662;179583661;179583660
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-66
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1291
• Predicted PPI site: I

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	rs757252230	-0.437	0.973	N	0.5	0.524	0.597483089494	gnomAD-2.1.1	3.26E-05	None	None	None	None	I	None	4.18E-05	0	None	0	0	None	0	None	0	6.34E-05	0
V/L	rs757252230	-0.437	0.973	N	0.5	0.524	0.597483089494	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	8.82E-05	0	0
V/L	rs757252230	-0.437	0.973	N	0.5	0.524	0.597483089494	gnomAD-4.0.0	8.12931E-05	None	None	None	None	I	None	1.33601E-05	0	None	0	0	None	0	0	1.06047E-04	0	8.01462E-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	0.2229	likely_benign	0.215	benign	-2.044	Highly Destabilizing	0.333	N	0.271	neutral	N	0.491234351	None	None	I
V/C	0.8486	likely_pathogenic	0.8427	pathogenic	-1.422	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	I
V/D	0.6726	likely_pathogenic	0.6674	pathogenic	-2.712	Highly Destabilizing	0.998	D	0.701	prob.neutral	D	0.554855617	None	None	I
V/E	0.5624	ambiguous	0.5892	pathogenic	-2.522	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
V/F	0.2735	likely_benign	0.3029	benign	-1.264	Destabilizing	0.999	D	0.65	neutral	D	0.536155477	None	None	I
V/G	0.3116	likely_benign	0.2855	benign	-2.538	Highly Destabilizing	0.989	D	0.676	prob.neutral	D	0.531636027	None	None	I
V/H	0.837	likely_pathogenic	0.859	pathogenic	-2.278	Highly Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
V/I	0.0969	likely_benign	0.099	benign	-0.679	Destabilizing	0.987	D	0.481	neutral	N	0.4921057	None	None	I
V/K	0.6306	likely_pathogenic	0.6716	pathogenic	-1.998	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	I
V/L	0.2826	likely_benign	0.3169	benign	-0.679	Destabilizing	0.973	D	0.5	neutral	N	0.498564161	None	None	I
V/M	0.2161	likely_benign	0.2281	benign	-0.537	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	I
V/N	0.5919	likely_pathogenic	0.5988	pathogenic	-2.229	Highly Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
V/P	0.9388	likely_pathogenic	0.9402	pathogenic	-1.107	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
V/Q	0.6213	likely_pathogenic	0.6664	pathogenic	-2.129	Highly Destabilizing	1.0	D	0.652	neutral	None	None	None	None	I
V/R	0.5958	likely_pathogenic	0.6456	pathogenic	-1.674	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
V/S	0.3937	ambiguous	0.3969	ambiguous	-2.774	Highly Destabilizing	0.983	D	0.629	neutral	None	None	None	None	I
V/T	0.2754	likely_benign	0.268	benign	-2.459	Highly Destabilizing	0.992	D	0.547	neutral	None	None	None	None	I
V/W	0.9284	likely_pathogenic	0.941	pathogenic	-1.811	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
V/Y	0.7222	likely_pathogenic	0.7585	pathogenic	-1.416	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I

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.