TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15154	45685;45686;45687	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
N2AB	13513	40762;40763;40764	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
N2A	12586	37981;37982;37983	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
N2B	6089	18490;18491;18492	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
Novex-1	6214	18865;18866;18867	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
Novex-2	6281	19066;19067;19068	chr2:178621258;178621257;178621256	chr2:179485985;179485984;179485983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-103
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1923
• 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
R/K	None	None	0.001	N	0.148	0.125	0.12205267543	gnomAD-4.0.0	1.36954E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79982E-06	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
R/A	0.8034	likely_pathogenic	0.7129	pathogenic	-1.404	Destabilizing	0.495	N	0.517	neutral	None	None	None	None	N
R/C	0.4102	ambiguous	0.3465	ambiguous	-1.295	Destabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
R/D	0.9425	likely_pathogenic	0.9045	pathogenic	-0.253	Destabilizing	0.704	D	0.683	prob.neutral	None	None	None	None	N
R/E	0.7357	likely_pathogenic	0.6479	pathogenic	-0.075	Destabilizing	0.329	N	0.566	neutral	None	None	None	None	N
R/F	0.7964	likely_pathogenic	0.7668	pathogenic	-1.088	Destabilizing	0.807	D	0.711	prob.delet.	None	None	None	None	N
R/G	0.761	likely_pathogenic	0.6571	pathogenic	-1.744	Destabilizing	0.642	D	0.603	neutral	N	0.517000873	None	None	N
R/H	0.2062	likely_benign	0.1942	benign	-2.021	Highly Destabilizing	0.981	D	0.619	neutral	None	None	None	None	N
R/I	0.4225	ambiguous	0.3636	ambiguous	-0.458	Destabilizing	0.543	D	0.691	prob.neutral	None	None	None	None	N
R/K	0.1178	likely_benign	0.1103	benign	-0.956	Destabilizing	0.001	N	0.148	neutral	N	0.379704166	None	None	N
R/L	0.4245	ambiguous	0.3523	ambiguous	-0.458	Destabilizing	0.007	N	0.437	neutral	None	None	None	None	N
R/M	0.4709	ambiguous	0.4075	ambiguous	-0.818	Destabilizing	0.863	D	0.649	neutral	D	0.611284029	None	None	N
R/N	0.864	likely_pathogenic	0.8242	pathogenic	-0.72	Destabilizing	0.704	D	0.606	neutral	None	None	None	None	N
R/P	0.9904	likely_pathogenic	0.9836	pathogenic	-0.756	Destabilizing	0.944	D	0.691	prob.neutral	None	None	None	None	N
R/Q	0.1935	likely_benign	0.1682	benign	-0.762	Destabilizing	0.704	D	0.595	neutral	None	None	None	None	N
R/S	0.8743	likely_pathogenic	0.812	pathogenic	-1.637	Destabilizing	0.642	D	0.597	neutral	N	0.446985742	None	None	N
R/T	0.6824	likely_pathogenic	0.5707	pathogenic	-1.238	Destabilizing	0.642	D	0.606	neutral	N	0.446985742	None	None	N
R/V	0.5812	likely_pathogenic	0.5112	ambiguous	-0.756	Destabilizing	0.543	D	0.625	neutral	None	None	None	None	N
R/W	0.3723	ambiguous	0.3233	benign	-0.664	Destabilizing	0.013	N	0.481	neutral	N	0.490047739	None	None	N
R/Y	0.6279	likely_pathogenic	0.5923	pathogenic	-0.451	Destabilizing	0.807	D	0.688	prob.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.