TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14373	43342;43343;43344	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
N2AB	12732	38419;38420;38421	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
N2A	11805	35638;35639;35640	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
N2B	5308	16147;16148;16149	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
Novex-1	5433	16522;16523;16524	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
Novex-2	5500	16723;16724;16725	chr2:178633014;178633013;178633012	chr2:179497741;179497740;179497739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-94
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.1286
• 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
H/N	rs1216345717	None	0.997	D	0.596	0.42	0.286081765059	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/N	rs1216345717	None	0.997	D	0.596	0.42	0.286081765059	gnomAD-4.0.0	6.57557E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47093E-05	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
H/A	0.9838	likely_pathogenic	0.9722	pathogenic	-2.126	Highly Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
H/C	0.8269	likely_pathogenic	0.783	pathogenic	-1.223	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
H/D	0.9843	likely_pathogenic	0.9769	pathogenic	-2.169	Highly Destabilizing	0.999	D	0.774	deleterious	D	0.619840274	None	None	N
H/E	0.9876	likely_pathogenic	0.9778	pathogenic	-1.925	Destabilizing	0.998	D	0.566	neutral	None	None	None	None	N
H/F	0.9004	likely_pathogenic	0.8812	pathogenic	-0.113	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
H/G	0.9834	likely_pathogenic	0.9773	pathogenic	-2.562	Highly Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
H/I	0.9716	likely_pathogenic	0.9626	pathogenic	-0.787	Destabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
H/K	0.9685	likely_pathogenic	0.9379	pathogenic	-1.003	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
H/L	0.8552	likely_pathogenic	0.8282	pathogenic	-0.787	Destabilizing	0.999	D	0.84	deleterious	D	0.575106481	None	None	N
H/M	0.9648	likely_pathogenic	0.9577	pathogenic	-1.05	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
H/N	0.8047	likely_pathogenic	0.7644	pathogenic	-2.062	Highly Destabilizing	0.997	D	0.596	neutral	D	0.619840274	None	None	N
H/P	0.9894	likely_pathogenic	0.9882	pathogenic	-1.23	Destabilizing	0.999	D	0.843	deleterious	D	0.619840274	None	None	N
H/Q	0.9394	likely_pathogenic	0.8867	pathogenic	-1.613	Destabilizing	0.999	D	0.805	deleterious	N	0.478675707	None	None	N
H/R	0.9176	likely_pathogenic	0.8233	pathogenic	-1.054	Destabilizing	0.999	D	0.761	deleterious	N	0.444895962	None	None	N
H/S	0.9659	likely_pathogenic	0.9507	pathogenic	-2.279	Highly Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
H/T	0.9835	likely_pathogenic	0.9765	pathogenic	-1.899	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
H/V	0.9671	likely_pathogenic	0.9559	pathogenic	-1.23	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
H/W	0.9181	likely_pathogenic	0.9014	pathogenic	0.624	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
H/Y	0.6064	likely_pathogenic	0.5556	ambiguous	0.271	Stabilizing	0.997	D	0.613	neutral	D	0.540266218	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.