TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30250	90973;90974;90975	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
N2AB	28609	86050;86051;86052	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
N2A	27682	83269;83270;83271	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
N2B	21185	63778;63779;63780	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
Novex-1	21310	64153;64154;64155	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
Novex-2	21377	64354;64355;64356	chr2:178552152;178552151;178552150	chr2:179416879;179416878;179416877
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: Fn3-108
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.9437
• 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/A	rs776305858	0.078	0.052	N	0.351	0.204	0.308278614506	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/A	rs776305858	0.078	0.052	N	0.351	0.204	0.308278614506	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
E/A	rs776305858	0.078	0.052	N	0.351	0.204	0.308278614506	gnomAD-4.0.0	2.56219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.68075E-05	0
E/K	rs200651247	0.716	0.001	N	0.129	0.202	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	8.27E-05	8.49E-05	None	0	0	None	0	None	0	2.35E-05	0
E/K	rs200651247	0.716	0.001	N	0.129	0.202	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	5.88E-05	0	0
E/K	rs200651247	0.716	0.001	N	0.129	0.202	None	gnomAD-4.0.0	1.12163E-04	None	None	None	None	N	None	1.33476E-05	6.67022E-05	None	0	0	None	0	0	1.4409E-04	0	9.60584E-05

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	0.1177	likely_benign	0.1235	benign	-0.049	Destabilizing	0.052	N	0.351	neutral	N	0.430977247	None	None	N
E/C	0.6957	likely_pathogenic	0.7399	pathogenic	-0.086	Destabilizing	0.935	D	0.398	neutral	None	None	None	None	N
E/D	0.0818	likely_benign	0.088	benign	-0.275	Destabilizing	None	N	0.14	neutral	N	0.479077839	None	None	N
E/F	0.6271	likely_pathogenic	0.6829	pathogenic	-0.087	Destabilizing	0.791	D	0.362	neutral	None	None	None	None	N
E/G	0.1645	likely_benign	0.1669	benign	-0.173	Destabilizing	0.117	N	0.446	neutral	N	0.494124649	None	None	N
E/H	0.3679	ambiguous	0.3969	ambiguous	0.425	Stabilizing	0.555	D	0.317	neutral	None	None	None	None	N
E/I	0.2277	likely_benign	0.2378	benign	0.219	Stabilizing	0.555	D	0.389	neutral	None	None	None	None	N
E/K	0.1403	likely_benign	0.1377	benign	0.465	Stabilizing	0.001	N	0.129	neutral	N	0.419778819	None	None	N
E/L	0.2568	likely_benign	0.2768	benign	0.219	Stabilizing	0.149	N	0.4	neutral	None	None	None	None	N
E/M	0.3487	ambiguous	0.3684	ambiguous	0.069	Stabilizing	0.935	D	0.366	neutral	None	None	None	None	N
E/N	0.1736	likely_benign	0.1945	benign	0.227	Stabilizing	0.081	N	0.332	neutral	None	None	None	None	N
E/P	0.5065	ambiguous	0.5379	ambiguous	0.148	Stabilizing	0.555	D	0.345	neutral	None	None	None	None	N
E/Q	0.1378	likely_benign	0.1465	benign	0.24	Stabilizing	0.005	N	0.21	neutral	N	0.468015483	None	None	N
E/R	0.2348	likely_benign	0.2422	benign	0.653	Stabilizing	0.081	N	0.333	neutral	None	None	None	None	N
E/S	0.1426	likely_benign	0.1611	benign	0.092	Stabilizing	0.081	N	0.304	neutral	None	None	None	None	N
E/T	0.1585	likely_benign	0.1718	benign	0.2	Stabilizing	0.149	N	0.411	neutral	None	None	None	None	N
E/V	0.145	likely_benign	0.1528	benign	0.148	Stabilizing	0.211	N	0.419	neutral	N	0.489641549	None	None	N
E/W	0.7928	likely_pathogenic	0.8323	pathogenic	-0.035	Destabilizing	0.935	D	0.465	neutral	None	None	None	None	N
E/Y	0.4729	ambiguous	0.5333	ambiguous	0.138	Stabilizing	0.791	D	0.378	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.