TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31711	95356;95357;95358	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
N2AB	30070	90433;90434;90435	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
N2A	29143	87652;87653;87654	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
N2B	22646	68161;68162;68163	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
Novex-1	22771	68536;68537;68538	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
Novex-2	22838	68737;68738;68739	chr2:178546105;178546104;178546103	chr2:179410832;179410831;179410830
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-119
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2914
• 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
P/L	None	None	0.997	D	0.705	0.485	0.653323239085	gnomAD-4.0.0	6.88534E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.0413E-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
P/A	0.0869	likely_benign	0.103	benign	-1.125	Destabilizing	0.543	D	0.352	neutral	N	0.488174538	None	None	N
P/C	0.4556	ambiguous	0.5473	ambiguous	-0.631	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/D	0.5395	ambiguous	0.6423	pathogenic	-1.077	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
P/E	0.3085	likely_benign	0.3761	ambiguous	-1.173	Destabilizing	0.983	D	0.55	neutral	None	None	None	None	N
P/F	0.4642	ambiguous	0.5518	ambiguous	-1.176	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
P/G	0.3844	ambiguous	0.4605	ambiguous	-1.33	Destabilizing	0.992	D	0.577	neutral	None	None	None	None	N
P/H	0.239	likely_benign	0.2849	benign	-0.895	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
P/I	0.2483	likely_benign	0.3088	benign	-0.7	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
P/K	0.2739	likely_benign	0.3344	benign	-0.899	Destabilizing	0.983	D	0.591	neutral	None	None	None	None	N
P/L	0.1432	likely_benign	0.1743	benign	-0.7	Destabilizing	0.997	D	0.705	prob.neutral	D	0.528314896	None	None	N
P/M	0.3198	likely_benign	0.3868	ambiguous	-0.392	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
P/N	0.3853	ambiguous	0.4884	ambiguous	-0.505	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
P/Q	0.1813	likely_benign	0.2218	benign	-0.823	Destabilizing	0.889	D	0.333	neutral	N	0.493271701	None	None	N
P/R	0.181	likely_benign	0.2111	benign	-0.271	Destabilizing	0.997	D	0.69	prob.neutral	N	0.512946119	None	None	N
P/S	0.1606	likely_benign	0.2026	benign	-0.889	Destabilizing	0.978	D	0.531	neutral	N	0.4721028	None	None	N
P/T	0.1374	likely_benign	0.1683	benign	-0.895	Destabilizing	0.997	D	0.615	neutral	N	0.51071762	None	None	N
P/V	0.1717	likely_benign	0.2067	benign	-0.807	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
P/W	0.7243	likely_pathogenic	0.7921	pathogenic	-1.245	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
P/Y	0.4663	ambiguous	0.5545	ambiguous	-0.989	Destabilizing	1.0	D	0.771	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.