TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21417	64474;64475;64476	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
N2AB	19776	59551;59552;59553	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
N2A	18849	56770;56771;56772	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
N2B	12352	37279;37280;37281	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
Novex-1	12477	37654;37655;37656	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
Novex-2	12544	37855;37856;37857	chr2:178586652;178586651;178586650	chr2:179451379;179451378;179451377
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: Fn3-43
• Domain position: 52
• Structural Position: 67
• Q(SASA): 0.6868
• 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/D	rs879230654	None	0.625	N	0.471	0.161	0.26547132957	gnomAD-4.0.0	1.36892E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7995E-06	0	0
E/Q	None	None	0.051	N	0.215	0.135	0.177238962908	gnomAD-4.0.0	6.84448E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15955E-05	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	0.1733	likely_benign	0.1604	benign	-0.641	Destabilizing	0.454	N	0.511	neutral	N	0.477368472	None	None	I
E/C	0.8665	likely_pathogenic	0.8459	pathogenic	0.018	Stabilizing	0.998	D	0.551	neutral	None	None	None	None	I
E/D	0.1684	likely_benign	0.1593	benign	-0.335	Destabilizing	0.625	D	0.471	neutral	N	0.476733754	None	None	I
E/F	0.8451	likely_pathogenic	0.8196	pathogenic	-0.534	Destabilizing	0.991	D	0.541	neutral	None	None	None	None	I
E/G	0.3154	likely_benign	0.2831	benign	-0.832	Destabilizing	0.801	D	0.515	neutral	N	0.507691379	None	None	I
E/H	0.57	likely_pathogenic	0.5127	ambiguous	-0.451	Destabilizing	0.974	D	0.535	neutral	None	None	None	None	I
E/I	0.3728	ambiguous	0.3665	ambiguous	-0.166	Destabilizing	0.974	D	0.547	neutral	None	None	None	None	I
E/K	0.2835	likely_benign	0.2449	benign	0.38	Stabilizing	0.454	N	0.473	neutral	N	0.42170719	None	None	I
E/L	0.4561	ambiguous	0.4266	ambiguous	-0.166	Destabilizing	0.842	D	0.537	neutral	None	None	None	None	I
E/M	0.5249	ambiguous	0.5181	ambiguous	0.124	Stabilizing	0.974	D	0.537	neutral	None	None	None	None	I
E/N	0.3029	likely_benign	0.2766	benign	-0.006	Destabilizing	0.842	D	0.468	neutral	None	None	None	None	I
E/P	0.3345	likely_benign	0.277	benign	-0.306	Destabilizing	0.007	N	0.267	neutral	None	None	None	None	I
E/Q	0.1641	likely_benign	0.152	benign	0.026	Stabilizing	0.051	N	0.215	neutral	N	0.477829832	None	None	I
E/R	0.4036	ambiguous	0.3565	ambiguous	0.452	Stabilizing	0.728	D	0.477	neutral	None	None	None	None	I
E/S	0.2304	likely_benign	0.2111	benign	-0.142	Destabilizing	0.172	N	0.227	neutral	None	None	None	None	I
E/T	0.2086	likely_benign	0.2066	benign	0.027	Stabilizing	0.728	D	0.494	neutral	None	None	None	None	I
E/V	0.213	likely_benign	0.2111	benign	-0.306	Destabilizing	0.891	D	0.529	neutral	N	0.462745736	None	None	I
E/W	0.9438	likely_pathogenic	0.9273	pathogenic	-0.335	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	I
E/Y	0.729	likely_pathogenic	0.6769	pathogenic	-0.278	Destabilizing	0.991	D	0.55	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.