TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7977	24154;24155;24156	chr2:178719563;178719562;178719561	chr2:179584290;179584289;179584288
N2AB	7660	23203;23204;23205	chr2:178719563;178719562;178719561	chr2:179584290;179584289;179584288
N2A	6733	20422;20423;20424	chr2:178719563;178719562;178719561	chr2:179584290;179584289;179584288
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-64
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4996
• 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/Q	rs1340162231	None	0.68	N	0.354	0.266	0.139678290688	gnomAD-4.0.0	1.37764E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81001E-06	0	0
H/R	rs1357770681	None	0.68	N	0.342	0.242	0.315314060047	gnomAD-4.0.0	2.06622E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71478E-06	0	0
H/Y	None	None	0.006	N	0.079	0.259	0.286081765059	gnomAD-4.0.0	1.61498E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91189E-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
H/A	0.1859	likely_benign	0.187	benign	-0.306	Destabilizing	0.098	N	0.312	neutral	None	None	None	None	N
H/C	0.195	likely_benign	0.2006	benign	0.325	Stabilizing	0.968	D	0.509	neutral	None	None	None	None	N
H/D	0.0996	likely_benign	0.0903	benign	0.097	Stabilizing	None	N	0.141	neutral	N	0.422966345	None	None	N
H/E	0.1625	likely_benign	0.1552	benign	0.139	Stabilizing	0.111	N	0.215	neutral	None	None	None	None	N
H/F	0.2515	likely_benign	0.254	benign	0.396	Stabilizing	0.223	N	0.448	neutral	None	None	None	None	N
H/G	0.272	likely_benign	0.2608	benign	-0.612	Destabilizing	0.365	N	0.351	neutral	None	None	None	None	N
H/I	0.2191	likely_benign	0.2174	benign	0.493	Stabilizing	0.008	N	0.297	neutral	None	None	None	None	N
H/K	0.2009	likely_benign	0.1955	benign	-0.236	Destabilizing	0.365	N	0.39	neutral	None	None	None	None	N
H/L	0.1041	likely_benign	0.0994	benign	0.493	Stabilizing	0.039	N	0.33	neutral	N	0.483745445	None	None	N
H/M	0.359	ambiguous	0.3569	ambiguous	0.374	Stabilizing	0.908	D	0.555	neutral	None	None	None	None	N
H/N	0.0664	likely_benign	0.0657	benign	-0.093	Destabilizing	0.178	N	0.311	neutral	N	0.4385118	None	None	N
H/P	0.5489	ambiguous	0.4733	ambiguous	0.251	Stabilizing	0.68	D	0.515	neutral	N	0.482325422	None	None	N
H/Q	0.1238	likely_benign	0.1183	benign	0.02	Stabilizing	0.68	D	0.354	neutral	N	0.407764819	None	None	N
H/R	0.0966	likely_benign	0.0933	benign	-0.662	Destabilizing	0.68	D	0.342	neutral	N	0.470104144	None	None	N
H/S	0.1412	likely_benign	0.1383	benign	-0.183	Destabilizing	0.111	N	0.288	neutral	None	None	None	None	N
H/T	0.1584	likely_benign	0.1605	benign	-0.044	Destabilizing	0.003	N	0.185	neutral	None	None	None	None	N
H/V	0.1681	likely_benign	0.167	benign	0.251	Stabilizing	0.003	N	0.277	neutral	None	None	None	None	N
H/W	0.3839	ambiguous	0.3691	ambiguous	0.539	Stabilizing	0.968	D	0.504	neutral	None	None	None	None	N
H/Y	0.0895	likely_benign	0.0893	benign	0.801	Stabilizing	0.006	N	0.079	neutral	N	0.48426552	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.