TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31465	94618;94619;94620	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
N2AB	29824	89695;89696;89697	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
N2A	28897	86914;86915;86916	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
N2B	22400	67423;67424;67425	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
Novex-1	22525	67798;67799;67800	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
Novex-2	22592	67999;68000;68001	chr2:178547132;178547131;178547130	chr2:179411859;179411858;179411857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-117
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.6829
• Predicted PPI site: I

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/K	rs752194452	0.288	0.977	N	0.598	0.386	0.286848849266	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.34E-05	0
E/K	rs752194452	0.288	0.977	N	0.598	0.386	0.286848849266	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	8.82E-05	0	0
E/K	rs752194452	0.288	0.977	N	0.598	0.386	0.286848849266	gnomAD-4.0.0	5.57718E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.9333E-06	2.19563E-05	0
E/Q	None	None	0.997	N	0.637	0.299	0.218112801441	gnomAD-4.0.0	2.05261E-06	None	None	None	None	I	None	0	0	None	0	2.51902E-05	None	1.87259E-05	0	8.99476E-07	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	0.1424	likely_benign	0.1617	benign	-0.389	Destabilizing	0.977	D	0.665	neutral	N	0.454680826	None	None	I
E/C	0.7694	likely_pathogenic	0.7983	pathogenic	-0.361	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
E/D	0.0745	likely_benign	0.0772	benign	-0.404	Destabilizing	0.117	N	0.223	neutral	N	0.438441937	None	None	I
E/F	0.6851	likely_pathogenic	0.741	pathogenic	-0.05	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
E/G	0.1503	likely_benign	0.1809	benign	-0.614	Destabilizing	0.993	D	0.641	neutral	N	0.467956768	None	None	I
E/H	0.4011	ambiguous	0.4611	ambiguous	0.357	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
E/I	0.4316	ambiguous	0.4799	ambiguous	0.183	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
E/K	0.248	likely_benign	0.3245	benign	0.072	Stabilizing	0.977	D	0.598	neutral	N	0.471034359	None	None	I
E/L	0.3966	ambiguous	0.447	ambiguous	0.183	Stabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	I
E/M	0.486	ambiguous	0.5308	ambiguous	0.084	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/N	0.1803	likely_benign	0.2124	benign	-0.333	Destabilizing	0.99	D	0.698	prob.neutral	None	None	None	None	I
E/P	0.7462	likely_pathogenic	0.7768	pathogenic	0.012	Stabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
E/Q	0.1485	likely_benign	0.172	benign	-0.257	Destabilizing	0.997	D	0.637	neutral	N	0.481251352	None	None	I
E/R	0.3468	ambiguous	0.4305	ambiguous	0.472	Stabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
E/S	0.1511	likely_benign	0.1791	benign	-0.522	Destabilizing	0.983	D	0.634	neutral	None	None	None	None	I
E/T	0.2033	likely_benign	0.2301	benign	-0.331	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
E/V	0.2545	likely_benign	0.2895	benign	0.012	Stabilizing	0.997	D	0.711	prob.delet.	N	0.486985246	None	None	I
E/W	0.8838	likely_pathogenic	0.9122	pathogenic	0.146	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
E/Y	0.5343	ambiguous	0.5949	pathogenic	0.199	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I

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.