TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6869	20830;20831;20832	chr2:178725599;178725598;178725597	chr2:179590326;179590325;179590324
N2AB	6552	19879;19880;19881	chr2:178725599;178725598;178725597	chr2:179590326;179590325;179590324
N2A	5625	17098;17099;17100	chr2:178725599;178725598;178725597	chr2:179590326;179590325;179590324
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3562
• 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	rs746830456	0.645	0.379	N	0.369	0.116	0.166414681773	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.8E-05	1.68577E-04
E/K	rs746830456	0.645	0.379	N	0.369	0.116	0.166414681773	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs746830456	0.645	0.379	N	0.369	0.116	0.166414681773	gnomAD-4.0.0	7.45328E-06	None	None	None	None	I	None	1.33804E-05	0	None	0	0	None	0	0	8.48915E-06	1.10725E-05	0
E/Q	rs746830456	None	0.099	N	0.343	0.079	0.0846915920261	gnomAD-4.0.0	6.85897E-07	None	None	None	None	I	None	3.00192E-05	0	None	0	0	None	0	0	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	0.1493	likely_benign	0.126	benign	-0.551	Destabilizing	0.549	D	0.298	neutral	N	0.491348101	None	None	I
E/C	0.7782	likely_pathogenic	0.7477	pathogenic	-0.229	Destabilizing	0.992	D	0.499	neutral	None	None	None	None	I
E/D	0.1099	likely_benign	0.0961	benign	-0.573	Destabilizing	0.004	N	0.333	neutral	N	0.443337964	None	None	I
E/F	0.5901	likely_pathogenic	0.5244	ambiguous	-0.275	Destabilizing	0.85	D	0.44	neutral	None	None	None	None	I
E/G	0.1332	likely_benign	0.1196	benign	-0.793	Destabilizing	0.004	N	0.281	neutral	N	0.50829352	None	None	I
E/H	0.3292	likely_benign	0.312	benign	-0.101	Destabilizing	0.92	D	0.314	neutral	None	None	None	None	I
E/I	0.2889	likely_benign	0.2368	benign	0.068	Stabilizing	0.92	D	0.437	neutral	None	None	None	None	I
E/K	0.0851	likely_benign	0.0871	benign	0.063	Stabilizing	0.379	N	0.369	neutral	N	0.493382782	None	None	I
E/L	0.28	likely_benign	0.2396	benign	0.068	Stabilizing	0.85	D	0.42	neutral	None	None	None	None	I
E/M	0.3079	likely_benign	0.2686	benign	0.186	Stabilizing	0.992	D	0.421	neutral	None	None	None	None	I
E/N	0.1713	likely_benign	0.1406	benign	-0.35	Destabilizing	0.447	N	0.338	neutral	None	None	None	None	I
E/P	0.7662	likely_pathogenic	0.7661	pathogenic	-0.118	Destabilizing	0.92	D	0.337	neutral	None	None	None	None	I
E/Q	0.0939	likely_benign	0.0907	benign	-0.298	Destabilizing	0.099	N	0.343	neutral	N	0.461078363	None	None	I
E/R	0.1655	likely_benign	0.173	benign	0.358	Stabilizing	0.85	D	0.339	neutral	None	None	None	None	I
E/S	0.1556	likely_benign	0.132	benign	-0.525	Destabilizing	0.447	N	0.309	neutral	None	None	None	None	I
E/T	0.1906	likely_benign	0.1585	benign	-0.329	Destabilizing	0.617	D	0.325	neutral	None	None	None	None	I
E/V	0.1808	likely_benign	0.1536	benign	-0.118	Destabilizing	0.896	D	0.411	neutral	N	0.481094659	None	None	I
E/W	0.8086	likely_pathogenic	0.8069	pathogenic	-0.066	Destabilizing	0.026	N	0.414	neutral	None	None	None	None	I
E/Y	0.4366	ambiguous	0.4011	ambiguous	-0.024	Destabilizing	0.85	D	0.421	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.