TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25212	75859;75860;75861	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
N2AB	23571	70936;70937;70938	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
N2A	22644	68155;68156;68157	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
N2B	16147	48664;48665;48666	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
Novex-1	16272	49039;49040;49041	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
Novex-2	16339	49240;49241;49242	chr2:178570498;178570497;178570496	chr2:179435225;179435224;179435223
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: Fn3-71
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1085
• 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/A	None	None	0.052	N	0.677	0.196	0.400756358115	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
V/L	rs1707781335	None	None	N	0.319	0.047	0.149567049428	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.027E-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	0.3226	likely_benign	0.3819	ambiguous	-1.434	Destabilizing	0.052	N	0.677	prob.neutral	N	0.473831682	None	None	N
V/C	0.8304	likely_pathogenic	0.8676	pathogenic	-1.084	Destabilizing	0.935	D	0.757	deleterious	None	None	None	None	N
V/D	0.973	likely_pathogenic	0.9798	pathogenic	-1.401	Destabilizing	0.484	N	0.827	deleterious	N	0.492189427	None	None	N
V/E	0.9447	likely_pathogenic	0.9574	pathogenic	-1.227	Destabilizing	0.555	D	0.778	deleterious	None	None	None	None	N
V/F	0.4721	ambiguous	0.4763	ambiguous	-0.735	Destabilizing	0.317	N	0.772	deleterious	N	0.517849657	None	None	N
V/G	0.6901	likely_pathogenic	0.7445	pathogenic	-1.926	Destabilizing	0.484	N	0.79	deleterious	N	0.504306201	None	None	N
V/H	0.9739	likely_pathogenic	0.9812	pathogenic	-1.715	Destabilizing	0.935	D	0.815	deleterious	None	None	None	None	N
V/I	0.0776	likely_benign	0.0769	benign	-0.11	Destabilizing	None	N	0.194	neutral	N	0.424400779	None	None	N
V/K	0.9581	likely_pathogenic	0.9695	pathogenic	-1.192	Destabilizing	0.555	D	0.777	deleterious	None	None	None	None	N
V/L	0.1854	likely_benign	0.2002	benign	-0.11	Destabilizing	None	N	0.319	neutral	N	0.373539523	None	None	N
V/M	0.2547	likely_benign	0.2654	benign	-0.248	Destabilizing	0.38	N	0.653	neutral	None	None	None	None	N
V/N	0.9161	likely_pathogenic	0.9356	pathogenic	-1.356	Destabilizing	0.791	D	0.829	deleterious	None	None	None	None	N
V/P	0.6591	likely_pathogenic	0.7382	pathogenic	-0.518	Destabilizing	0.791	D	0.813	deleterious	None	None	None	None	N
V/Q	0.9398	likely_pathogenic	0.9556	pathogenic	-1.211	Destabilizing	0.791	D	0.806	deleterious	None	None	None	None	N
V/R	0.9369	likely_pathogenic	0.9543	pathogenic	-1.122	Destabilizing	0.555	D	0.829	deleterious	None	None	None	None	N
V/S	0.7227	likely_pathogenic	0.781	pathogenic	-2.003	Highly Destabilizing	0.262	N	0.765	deleterious	None	None	None	None	N
V/T	0.5053	ambiguous	0.57	pathogenic	-1.682	Destabilizing	0.149	N	0.733	prob.delet.	None	None	None	None	N
V/W	0.9715	likely_pathogenic	0.9773	pathogenic	-1.181	Destabilizing	0.935	D	0.8	deleterious	None	None	None	None	N
V/Y	0.9068	likely_pathogenic	0.9292	pathogenic	-0.748	Destabilizing	0.555	D	0.766	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.