TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7787	23584;23585;23586	chr2:178720403;178720402;178720401	chr2:179585130;179585129;179585128
N2AB	7470	22633;22634;22635	chr2:178720403;178720402;178720401	chr2:179585130;179585129;179585128
N2A	6543	19852;19853;19854	chr2:178720403;178720402;178720401	chr2:179585130;179585129;179585128
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-62
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1337
• 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
C/F	rs1332033261	None	0.954	N	0.797	0.356	0.7694930422	gnomAD-4.0.0	6.84853E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00051E-07	0	0
C/S	rs1332033261	-2.417	0.002	N	0.392	0.33	0.546736107678	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
C/S	rs1332033261	-2.417	0.002	N	0.392	0.33	0.546736107678	gnomAD-4.0.0	6.84853E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00051E-07	0	0
C/Y	None	None	0.954	N	0.779	0.369	0.728244352428	gnomAD-4.0.0	6.84853E-07	None	None	None	None	N	None	0	0	None	0	2.51965E-05	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
C/A	0.231	likely_benign	0.2157	benign	-2.122	Highly Destabilizing	0.002	N	0.113	neutral	None	None	None	None	N
C/D	0.875	likely_pathogenic	0.8581	pathogenic	-1.514	Destabilizing	0.561	D	0.693	prob.neutral	None	None	None	None	N
C/E	0.9457	likely_pathogenic	0.9399	pathogenic	-1.325	Destabilizing	0.561	D	0.693	prob.neutral	None	None	None	None	N
C/F	0.3112	likely_benign	0.2674	benign	-1.391	Destabilizing	0.954	D	0.797	deleterious	N	0.479454346	None	None	N
C/G	0.1239	likely_benign	0.1184	benign	-2.482	Highly Destabilizing	0.001	N	0.534	neutral	N	0.437127721	None	None	N
C/H	0.8118	likely_pathogenic	0.7983	pathogenic	-2.599	Highly Destabilizing	0.965	D	0.759	deleterious	None	None	None	None	N
C/I	0.4918	ambiguous	0.4647	ambiguous	-1.151	Destabilizing	0.561	D	0.71	prob.delet.	None	None	None	None	N
C/K	0.9703	likely_pathogenic	0.9658	pathogenic	-1.578	Destabilizing	0.561	D	0.695	prob.neutral	None	None	None	None	N
C/L	0.5073	ambiguous	0.4753	ambiguous	-1.151	Destabilizing	0.345	N	0.618	neutral	None	None	None	None	N
C/M	0.7002	likely_pathogenic	0.6706	pathogenic	0.188	Stabilizing	0.965	D	0.747	deleterious	None	None	None	None	N
C/N	0.7198	likely_pathogenic	0.6997	pathogenic	-1.926	Destabilizing	0.561	D	0.711	prob.delet.	None	None	None	None	N
C/P	0.9753	likely_pathogenic	0.974	pathogenic	-1.451	Destabilizing	0.722	D	0.771	deleterious	None	None	None	None	N
C/Q	0.8701	likely_pathogenic	0.8624	pathogenic	-1.62	Destabilizing	0.901	D	0.812	deleterious	None	None	None	None	N
C/R	0.8344	likely_pathogenic	0.8194	pathogenic	-1.695	Destabilizing	0.491	N	0.799	deleterious	N	0.488908787	None	None	N
C/S	0.1951	likely_benign	0.1806	benign	-2.352	Highly Destabilizing	0.002	N	0.392	neutral	N	0.442360182	None	None	N
C/T	0.323	likely_benign	0.2992	benign	-1.975	Destabilizing	0.007	N	0.415	neutral	None	None	None	None	N
C/V	0.3564	ambiguous	0.3383	benign	-1.451	Destabilizing	0.345	N	0.623	neutral	None	None	None	None	N
C/W	0.7913	likely_pathogenic	0.7514	pathogenic	-1.6	Destabilizing	0.987	D	0.727	prob.delet.	N	0.500683166	None	None	N
C/Y	0.5656	likely_pathogenic	0.5235	ambiguous	-1.542	Destabilizing	0.954	D	0.779	deleterious	N	0.494866515	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.