TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28720	86383;86384;86385	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
N2AB	27079	81460;81461;81462	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
N2A	26152	78679;78680;78681	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
N2B	19655	59188;59189;59190	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
Novex-1	19780	59563;59564;59565	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
Novex-2	19847	59764;59765;59766	chr2:178559974;178559973;178559972	chr2:179424701;179424700;179424699
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: Fn3-97
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.3643
• 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/Q	None	None	1.0	N	0.628	0.34	0.242244723065	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.1368	likely_benign	0.1342	benign	-1.011	Destabilizing	0.999	D	0.704	prob.neutral	D	0.524927558	None	None	N
E/C	0.8131	likely_pathogenic	0.8012	pathogenic	-0.545	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/D	0.2552	likely_benign	0.2652	benign	-1.184	Destabilizing	0.999	D	0.471	neutral	D	0.523772765	None	None	N
E/F	0.7891	likely_pathogenic	0.7802	pathogenic	-0.327	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/G	0.2299	likely_benign	0.2195	benign	-1.429	Destabilizing	1.0	D	0.754	deleterious	N	0.48255096	None	None	N
E/H	0.5118	ambiguous	0.4882	ambiguous	-0.643	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/I	0.3456	ambiguous	0.335	benign	0.151	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/K	0.1408	likely_benign	0.1341	benign	-0.903	Destabilizing	0.999	D	0.611	neutral	N	0.50764852	None	None	N
E/L	0.3979	ambiguous	0.3807	ambiguous	0.151	Stabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/M	0.4268	ambiguous	0.4156	ambiguous	0.726	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/N	0.2994	likely_benign	0.3052	benign	-1.391	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/P	0.4919	ambiguous	0.4967	ambiguous	-0.216	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.1188	likely_benign	0.1176	benign	-1.194	Destabilizing	1.0	D	0.628	neutral	N	0.480328632	None	None	N
E/R	0.2598	likely_benign	0.2424	benign	-0.627	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.2106	likely_benign	0.2022	benign	-1.816	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/T	0.2004	likely_benign	0.1882	benign	-1.46	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/V	0.1988	likely_benign	0.1948	benign	-0.216	Destabilizing	1.0	D	0.79	deleterious	N	0.518617662	None	None	N
E/W	0.9318	likely_pathogenic	0.9233	pathogenic	-0.083	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/Y	0.692	likely_pathogenic	0.6754	pathogenic	-0.074	Destabilizing	1.0	D	0.767	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.