TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29275	88048;88049;88050	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
N2AB	27634	83125;83126;83127	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
N2A	26707	80344;80345;80346	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
N2B	20210	60853;60854;60855	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
Novex-1	20335	61228;61229;61230	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
Novex-2	20402	61429;61430;61431	chr2:178557439;178557438;178557437	chr2:179422166;179422165;179422164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-101
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.115
• 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
E/Q	rs766410679	-1.028	0.31	D	0.373	0.213	0.229264304666	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	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
E/A	0.8201	likely_pathogenic	0.8096	pathogenic	-1.201	Destabilizing	0.826	D	0.588	neutral	D	0.531076827	None	None	N
E/C	0.9842	likely_pathogenic	0.9825	pathogenic	-0.553	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
E/D	0.8285	likely_pathogenic	0.7893	pathogenic	-1.824	Destabilizing	0.92	D	0.618	neutral	N	0.482942581	None	None	N
E/F	0.9874	likely_pathogenic	0.9843	pathogenic	-0.853	Destabilizing	0.982	D	0.745	deleterious	None	None	None	None	N
E/G	0.9314	likely_pathogenic	0.921	pathogenic	-1.603	Destabilizing	0.959	D	0.641	neutral	N	0.514746999	None	None	N
E/H	0.9638	likely_pathogenic	0.9557	pathogenic	-0.825	Destabilizing	0.991	D	0.662	neutral	None	None	None	None	N
E/I	0.9579	likely_pathogenic	0.9621	pathogenic	-0.047	Destabilizing	0.964	D	0.706	prob.neutral	None	None	None	None	N
E/K	0.9533	likely_pathogenic	0.9499	pathogenic	-1.384	Destabilizing	0.852	D	0.645	neutral	N	0.518453074	None	None	N
E/L	0.9482	likely_pathogenic	0.9516	pathogenic	-0.047	Destabilizing	0.046	N	0.585	neutral	None	None	None	None	N
E/M	0.9428	likely_pathogenic	0.9381	pathogenic	0.638	Stabilizing	0.982	D	0.718	prob.delet.	None	None	None	None	N
E/N	0.9741	likely_pathogenic	0.9693	pathogenic	-1.702	Destabilizing	0.991	D	0.64	neutral	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9996	pathogenic	-0.417	Destabilizing	0.997	D	0.645	neutral	None	None	None	None	N
E/Q	0.6123	likely_pathogenic	0.5841	pathogenic	-1.356	Destabilizing	0.31	N	0.373	neutral	D	0.523271333	None	None	N
E/R	0.9606	likely_pathogenic	0.9584	pathogenic	-1.284	Destabilizing	0.939	D	0.633	neutral	None	None	None	None	N
E/S	0.907	likely_pathogenic	0.8965	pathogenic	-2.269	Highly Destabilizing	0.939	D	0.631	neutral	None	None	None	None	N
E/T	0.9549	likely_pathogenic	0.9521	pathogenic	-1.886	Destabilizing	0.969	D	0.595	neutral	None	None	None	None	N
E/V	0.885	likely_pathogenic	0.8953	pathogenic	-0.417	Destabilizing	0.852	D	0.644	neutral	D	0.531837296	None	None	N
E/W	0.9963	likely_pathogenic	0.9953	pathogenic	-1.029	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/Y	0.985	likely_pathogenic	0.9813	pathogenic	-0.706	Destabilizing	0.997	D	0.717	prob.delet.	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.