TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17466	52621;52622;52623	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
N2AB	15825	47698;47699;47700	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
N2A	14898	44917;44918;44919	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
N2B	8401	25426;25427;25428	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
Novex-1	8526	25801;25802;25803	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
Novex-2	8593	26002;26003;26004	chr2:178608615;178608614;178608613	chr2:179473342;179473341;179473340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-14
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.8919
• 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
D/G	rs377156953	None	0.919	N	0.608	0.235	0.235664433957	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	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
D/A	0.8201	likely_pathogenic	0.7404	pathogenic	-0.403	Destabilizing	0.958	D	0.556	neutral	N	0.494964437	None	None	N
D/C	0.9567	likely_pathogenic	0.9375	pathogenic	-0.244	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
D/E	0.7414	likely_pathogenic	0.6684	pathogenic	-0.512	Destabilizing	0.824	D	0.531	neutral	N	0.466759115	None	None	N
D/F	0.9106	likely_pathogenic	0.8748	pathogenic	-0.217	Destabilizing	0.997	D	0.729	deleterious	None	None	None	None	N
D/G	0.8937	likely_pathogenic	0.8375	pathogenic	-0.644	Destabilizing	0.919	D	0.608	neutral	N	0.511915402	None	None	N
D/H	0.789	likely_pathogenic	0.7243	pathogenic	-0.198	Destabilizing	0.988	D	0.492	neutral	N	0.4981781	None	None	N
D/I	0.9032	likely_pathogenic	0.8462	pathogenic	0.199	Stabilizing	0.997	D	0.784	deleterious	None	None	None	None	N
D/K	0.9706	likely_pathogenic	0.9491	pathogenic	-0.168	Destabilizing	0.938	D	0.648	neutral	None	None	None	None	N
D/L	0.8598	likely_pathogenic	0.7893	pathogenic	0.199	Stabilizing	0.991	D	0.759	deleterious	None	None	None	None	N
D/M	0.9589	likely_pathogenic	0.9354	pathogenic	0.316	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
D/N	0.3089	likely_benign	0.2606	benign	-0.452	Destabilizing	0.06	N	0.198	neutral	N	0.412695344	None	None	N
D/P	0.9591	likely_pathogenic	0.9249	pathogenic	0.021	Stabilizing	0.997	D	0.553	neutral	None	None	None	None	N
D/Q	0.951	likely_pathogenic	0.9214	pathogenic	-0.395	Destabilizing	0.991	D	0.54	neutral	None	None	None	None	N
D/R	0.9766	likely_pathogenic	0.96	pathogenic	0.085	Stabilizing	0.991	D	0.693	prob.delet.	None	None	None	None	N
D/S	0.662	likely_pathogenic	0.5924	pathogenic	-0.591	Destabilizing	0.938	D	0.545	neutral	None	None	None	None	N
D/T	0.8822	likely_pathogenic	0.8225	pathogenic	-0.411	Destabilizing	0.938	D	0.649	prob.neutral	None	None	None	None	N
D/V	0.8193	likely_pathogenic	0.7321	pathogenic	0.021	Stabilizing	0.996	D	0.78	deleterious	N	0.497311309	None	None	N
D/W	0.981	likely_pathogenic	0.9743	pathogenic	-0.075	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
D/Y	0.5291	ambiguous	0.4598	ambiguous	-0.004	Destabilizing	0.996	D	0.745	deleterious	N	0.483902081	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.