TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29177	87754;87755;87756	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
N2AB	27536	82831;82832;82833	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
N2A	26609	80050;80051;80052	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
N2B	20112	60559;60560;60561	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
Novex-1	20237	60934;60935;60936	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
Novex-2	20304	61135;61136;61137	chr2:178557825;178557824;178557823	chr2:179422552;179422551;179422550
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-100
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.179
• 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
K/E	rs765090108	-2.148	0.928	N	0.721	0.31	0.318540980066	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/E	rs765090108	-2.148	0.928	N	0.721	0.31	0.318540980066	gnomAD-4.0.0	6.84163E-07	None	None	None	None	N	None	0	2.23594E-05	None	0	0	None	0	0	0	0	0
K/N	rs1228451562	None	0.978	N	0.855	0.368	0.252162846088	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1228451562	None	0.978	N	0.855	0.368	0.252162846088	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46985E-05	0	0
K/Q	rs765090108	None	0.978	N	0.855	0.296	0.270001397563	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-06	0	0
K/R	rs762172006	-0.796	0.085	N	0.417	0.094	0.256283259241	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
K/R	rs762172006	-0.796	0.085	N	0.417	0.094	0.256283259241	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79886E-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
K/A	0.9133	likely_pathogenic	0.9487	pathogenic	-1.394	Destabilizing	0.944	D	0.709	prob.delet.	None	None	None	None	N
K/C	0.7882	likely_pathogenic	0.8472	pathogenic	-1.326	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/D	0.9952	likely_pathogenic	0.9972	pathogenic	-2.08	Highly Destabilizing	0.992	D	0.833	deleterious	None	None	None	None	N
K/E	0.8205	likely_pathogenic	0.8866	pathogenic	-1.747	Destabilizing	0.928	D	0.721	prob.delet.	N	0.513021798	None	None	N
K/F	0.948	likely_pathogenic	0.9676	pathogenic	-0.76	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
K/G	0.9555	likely_pathogenic	0.9757	pathogenic	-1.877	Destabilizing	0.983	D	0.787	deleterious	None	None	None	None	N
K/H	0.633	likely_pathogenic	0.7204	pathogenic	-1.452	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
K/I	0.7908	likely_pathogenic	0.8734	pathogenic	-0.002	Destabilizing	0.989	D	0.859	deleterious	N	0.475443708	None	None	N
K/L	0.6316	likely_pathogenic	0.7603	pathogenic	-0.002	Destabilizing	0.983	D	0.787	deleterious	None	None	None	None	N
K/M	0.4431	ambiguous	0.5644	pathogenic	-0.38	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
K/N	0.9701	likely_pathogenic	0.9824	pathogenic	-1.821	Destabilizing	0.978	D	0.855	deleterious	N	0.513021798	None	None	N
K/P	0.9979	likely_pathogenic	0.9987	pathogenic	-0.449	Destabilizing	0.997	D	0.846	deleterious	None	None	None	None	N
K/Q	0.2499	likely_benign	0.3284	benign	-1.4	Destabilizing	0.978	D	0.855	deleterious	N	0.484548742	None	None	N
K/R	0.1079	likely_benign	0.1257	benign	-0.577	Destabilizing	0.085	N	0.417	neutral	N	0.496796808	None	None	N
K/S	0.9286	likely_pathogenic	0.9614	pathogenic	-2.317	Highly Destabilizing	0.944	D	0.749	deleterious	None	None	None	None	N
K/T	0.7985	likely_pathogenic	0.8763	pathogenic	-1.712	Destabilizing	0.978	D	0.808	deleterious	N	0.492004254	None	None	N
K/V	0.7349	likely_pathogenic	0.8271	pathogenic	-0.449	Destabilizing	0.992	D	0.821	deleterious	None	None	None	None	N
K/W	0.9073	likely_pathogenic	0.938	pathogenic	-0.793	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
K/Y	0.8622	likely_pathogenic	0.9036	pathogenic	-0.446	Destabilizing	0.997	D	0.855	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.