TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8327	25204;25205;25206	chr2:178718027;178718026;178718025	chr2:179582754;179582753;179582752
N2AB	8010	24253;24254;24255	chr2:178718027;178718026;178718025	chr2:179582754;179582753;179582752
N2A	7083	21472;21473;21474	chr2:178718027;178718026;178718025	chr2:179582754;179582753;179582752
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-68
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2791
• Predicted PPI site: I

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
D/V	None	None	0.97	N	0.437	0.41	0.647137792213	gnomAD-4.0.0	1.5914E-06	None	None	None	None	I	None	0	0	None	0	2.77285E-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
D/A	0.2362	likely_benign	0.2879	benign	-0.423	Destabilizing	0.879	D	0.396	neutral	N	0.500349693	None	None	I
D/C	0.7647	likely_pathogenic	0.8382	pathogenic	-0.183	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	I
D/E	0.2121	likely_benign	0.2261	benign	-0.609	Destabilizing	0.001	N	0.164	neutral	N	0.454441258	None	None	I
D/F	0.6673	likely_pathogenic	0.7318	pathogenic	-0.079	Destabilizing	0.996	D	0.446	neutral	None	None	None	None	I
D/G	0.2393	likely_benign	0.2782	benign	-0.745	Destabilizing	0.016	N	0.223	neutral	N	0.501216485	None	None	I
D/H	0.376	ambiguous	0.4439	ambiguous	-0.308	Destabilizing	0.066	N	0.291	neutral	N	0.511529479	None	None	I
D/I	0.4999	ambiguous	0.592	pathogenic	0.414	Stabilizing	0.996	D	0.456	neutral	None	None	None	None	I
D/K	0.5395	ambiguous	0.6083	pathogenic	-0.394	Destabilizing	0.945	D	0.31	neutral	None	None	None	None	I
D/L	0.4618	ambiguous	0.5343	ambiguous	0.414	Stabilizing	0.992	D	0.435	neutral	None	None	None	None	I
D/M	0.7051	likely_pathogenic	0.7599	pathogenic	0.747	Stabilizing	0.999	D	0.443	neutral	None	None	None	None	I
D/N	0.1276	likely_benign	0.142	benign	-0.767	Destabilizing	0.764	D	0.361	neutral	N	0.497386746	None	None	I
D/P	0.9194	likely_pathogenic	0.9475	pathogenic	0.16	Stabilizing	0.829	D	0.338	neutral	None	None	None	None	I
D/Q	0.4207	ambiguous	0.474	ambiguous	-0.617	Destabilizing	0.958	D	0.351	neutral	None	None	None	None	I
D/R	0.5304	ambiguous	0.6025	pathogenic	-0.171	Destabilizing	0.992	D	0.412	neutral	None	None	None	None	I
D/S	0.1443	likely_benign	0.1655	benign	-0.958	Destabilizing	0.906	D	0.317	neutral	None	None	None	None	I
D/T	0.3226	likely_benign	0.3585	ambiguous	-0.703	Destabilizing	0.811	D	0.339	neutral	None	None	None	None	I
D/V	0.3324	likely_benign	0.4058	ambiguous	0.16	Stabilizing	0.97	D	0.437	neutral	N	0.499677689	None	None	I
D/W	0.9337	likely_pathogenic	0.952	pathogenic	0.058	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	I
D/Y	0.3589	ambiguous	0.4381	ambiguous	0.126	Stabilizing	0.989	D	0.457	neutral	N	0.518436808	None	None	I

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.