TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15212	45859;45860;45861	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
N2AB	13571	40936;40937;40938	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
N2A	12644	38155;38156;38157	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
N2B	6147	18664;18665;18666	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
Novex-1	6272	19039;19040;19041	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
Novex-2	6339	19240;19241;19242	chr2:178620976;178620975;178620974	chr2:179485703;179485702;179485701
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-104
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2719
• 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
V/I	None	None	0.003	N	0.123	0.084	0.401042353794	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
V/A	0.1614	likely_benign	0.1763	benign	-1.103	Destabilizing	0.08	N	0.194	neutral	N	0.479844238	None	None	N
V/C	0.7795	likely_pathogenic	0.7487	pathogenic	-0.773	Destabilizing	0.965	D	0.36	neutral	None	None	None	None	N
V/D	0.3428	ambiguous	0.3527	ambiguous	-1.067	Destabilizing	0.491	N	0.443	neutral	N	0.506871151	None	None	N
V/E	0.2705	likely_benign	0.2703	benign	-1.119	Destabilizing	0.561	D	0.386	neutral	None	None	None	None	N
V/F	0.152	likely_benign	0.1394	benign	-0.903	Destabilizing	0.772	D	0.404	neutral	N	0.508941464	None	None	N
V/G	0.2571	likely_benign	0.2516	benign	-1.345	Destabilizing	0.001	N	0.299	neutral	N	0.495574785	None	None	N
V/H	0.4707	ambiguous	0.4677	ambiguous	-0.81	Destabilizing	0.991	D	0.407	neutral	None	None	None	None	N
V/I	0.0801	likely_benign	0.0851	benign	-0.569	Destabilizing	0.003	N	0.123	neutral	N	0.473486191	None	None	N
V/K	0.2852	likely_benign	0.2709	benign	-1.091	Destabilizing	0.561	D	0.407	neutral	None	None	None	None	N
V/L	0.1775	likely_benign	0.1817	benign	-0.569	Destabilizing	0.08	N	0.215	neutral	N	0.487852958	None	None	N
V/M	0.1404	likely_benign	0.1479	benign	-0.457	Destabilizing	0.818	D	0.397	neutral	None	None	None	None	N
V/N	0.1956	likely_benign	0.2105	benign	-0.853	Destabilizing	0.561	D	0.433	neutral	None	None	None	None	N
V/P	0.877	likely_pathogenic	0.8416	pathogenic	-0.711	Destabilizing	0.901	D	0.429	neutral	None	None	None	None	N
V/Q	0.286	likely_benign	0.2836	benign	-1.082	Destabilizing	0.901	D	0.405	neutral	None	None	None	None	N
V/R	0.2674	likely_benign	0.2477	benign	-0.459	Destabilizing	0.901	D	0.449	neutral	None	None	None	None	N
V/S	0.1575	likely_benign	0.1695	benign	-1.257	Destabilizing	0.209	N	0.372	neutral	None	None	None	None	N
V/T	0.1248	likely_benign	0.1405	benign	-1.214	Destabilizing	0.002	N	0.127	neutral	None	None	None	None	N
V/W	0.8305	likely_pathogenic	0.8006	pathogenic	-1.041	Destabilizing	0.991	D	0.441	neutral	None	None	None	None	N
V/Y	0.5373	ambiguous	0.5174	ambiguous	-0.779	Destabilizing	0.965	D	0.381	neutral	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.