TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7574	22945;22946;22947	chr2:178721943;178721942;178721941	chr2:179586670;179586669;179586668
N2AB	7257	21994;21995;21996	chr2:178721943;178721942;178721941	chr2:179586670;179586669;179586668
N2A	6330	19213;19214;19215	chr2:178721943;178721942;178721941	chr2:179586670;179586669;179586668
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-60
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0574
• 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
I/V	rs1017841481	-1.727	0.011	D	0.248	0.345	0.55842215	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
I/V	rs1017841481	-1.727	0.011	D	0.248	0.345	0.55842215	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.23E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs1017841481	-1.727	0.011	D	0.248	0.345	0.55842215	gnomAD-4.0.0	4.05965E-06	None	None	None	None	N	None	6.98666E-05	0	None	0	0	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
I/A	0.9728	likely_pathogenic	0.9822	pathogenic	-2.988	Highly Destabilizing	0.702	D	0.707	prob.neutral	None	None	None	None	N
I/C	0.9715	likely_pathogenic	0.9785	pathogenic	-2.272	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
I/D	0.9984	likely_pathogenic	0.9989	pathogenic	-3.555	Highly Destabilizing	0.996	D	0.89	deleterious	None	None	None	None	N
I/E	0.9964	likely_pathogenic	0.9975	pathogenic	-3.233	Highly Destabilizing	0.988	D	0.887	deleterious	None	None	None	None	N
I/F	0.672	likely_pathogenic	0.7583	pathogenic	-1.784	Destabilizing	0.968	D	0.729	prob.delet.	D	0.55507666	None	None	N
I/G	0.9939	likely_pathogenic	0.9962	pathogenic	-3.608	Highly Destabilizing	0.988	D	0.877	deleterious	None	None	None	None	N
I/H	0.9909	likely_pathogenic	0.9941	pathogenic	-3.221	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
I/K	0.9919	likely_pathogenic	0.994	pathogenic	-2.226	Highly Destabilizing	0.988	D	0.886	deleterious	None	None	None	None	N
I/L	0.2973	likely_benign	0.3338	benign	-1.121	Destabilizing	0.011	N	0.313	neutral	D	0.5608057	None	None	N
I/M	0.4453	ambiguous	0.5052	ambiguous	-1.33	Destabilizing	0.968	D	0.7	prob.neutral	D	0.5978557	None	None	N
I/N	0.9706	likely_pathogenic	0.9781	pathogenic	-2.91	Highly Destabilizing	0.995	D	0.887	deleterious	D	0.65034455	None	None	N
I/P	0.9959	likely_pathogenic	0.9974	pathogenic	-1.734	Destabilizing	0.996	D	0.888	deleterious	None	None	None	None	N
I/Q	0.9911	likely_pathogenic	0.9943	pathogenic	-2.572	Highly Destabilizing	0.996	D	0.901	deleterious	None	None	None	None	N
I/R	0.9885	likely_pathogenic	0.9919	pathogenic	-2.202	Highly Destabilizing	0.988	D	0.889	deleterious	None	None	None	None	N
I/S	0.9751	likely_pathogenic	0.9839	pathogenic	-3.529	Highly Destabilizing	0.984	D	0.838	deleterious	D	0.63432515	None	None	N
I/T	0.9783	likely_pathogenic	0.9853	pathogenic	-3.041	Highly Destabilizing	0.896	D	0.762	deleterious	D	0.63392156	None	None	N
I/V	0.1259	likely_benign	0.1383	benign	-1.734	Destabilizing	0.011	N	0.248	neutral	D	0.5755113	None	None	N
I/W	0.9913	likely_pathogenic	0.9945	pathogenic	-2.195	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
I/Y	0.956	likely_pathogenic	0.9723	pathogenic	-2.008	Highly Destabilizing	0.996	D	0.799	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.