TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7153	21682;21683;21684	chr2:178723643;178723642;178723641	chr2:179588370;179588369;179588368
N2AB	6836	20731;20732;20733	chr2:178723643;178723642;178723641	chr2:179588370;179588369;179588368
N2A	5909	17950;17951;17952	chr2:178723643;178723642;178723641	chr2:179588370;179588369;179588368
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-56
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.341
• 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
N/S	rs1287422733	-0.785	0.023	N	0.113	0.061	0.0846915920261	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	2.95E-05	None	0	0	None	0	None	0	0	0
N/S	rs1287422733	-0.785	0.023	N	0.113	0.061	0.0846915920261	gnomAD-4.0.0	1.60046E-06	None	None	None	None	N	None	0	2.3083E-05	None	0	0	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
N/A	0.2393	likely_benign	0.2334	benign	-0.812	Destabilizing	0.329	N	0.325	neutral	None	None	None	None	N
N/C	0.4483	ambiguous	0.4637	ambiguous	0.104	Stabilizing	0.995	D	0.308	neutral	None	None	None	None	N
N/D	0.1244	likely_benign	0.1274	benign	0.01	Stabilizing	0.006	N	0.123	neutral	N	0.460208784	None	None	N
N/E	0.3802	ambiguous	0.3692	ambiguous	0.084	Stabilizing	0.329	N	0.248	neutral	None	None	None	None	N
N/F	0.6301	likely_pathogenic	0.6279	pathogenic	-0.685	Destabilizing	0.807	D	0.387	neutral	None	None	None	None	N
N/G	0.3326	likely_benign	0.3254	benign	-1.124	Destabilizing	0.329	N	0.231	neutral	None	None	None	None	N
N/H	0.1544	likely_benign	0.157	benign	-0.854	Destabilizing	0.863	D	0.33	neutral	N	0.463529701	None	None	N
N/I	0.2934	likely_benign	0.2895	benign	-0.033	Destabilizing	0.863	D	0.385	neutral	N	0.490027746	None	None	N
N/K	0.3158	likely_benign	0.2998	benign	-0.097	Destabilizing	0.01	N	0.107	neutral	N	0.494014714	None	None	N
N/L	0.331	likely_benign	0.3176	benign	-0.033	Destabilizing	0.543	D	0.35	neutral	None	None	None	None	N
N/M	0.3438	ambiguous	0.33	benign	0.32	Stabilizing	0.981	D	0.294	neutral	None	None	None	None	N
N/P	0.4324	ambiguous	0.4238	ambiguous	-0.263	Destabilizing	0.828	D	0.359	neutral	None	None	None	None	N
N/Q	0.388	ambiguous	0.3773	ambiguous	-0.586	Destabilizing	0.704	D	0.262	neutral	None	None	None	None	N
N/R	0.3626	ambiguous	0.3482	ambiguous	-0.132	Destabilizing	0.543	D	0.173	neutral	None	None	None	None	N
N/S	0.1039	likely_benign	0.1032	benign	-0.671	Destabilizing	0.023	N	0.113	neutral	N	0.437793284	None	None	N
N/T	0.1251	likely_benign	0.1243	benign	-0.401	Destabilizing	0.023	N	0.123	neutral	N	0.430963313	None	None	N
N/V	0.3042	likely_benign	0.294	benign	-0.263	Destabilizing	0.704	D	0.361	neutral	None	None	None	None	N
N/W	0.7899	likely_pathogenic	0.7825	pathogenic	-0.468	Destabilizing	0.985	D	0.316	neutral	None	None	None	None	N
N/Y	0.189	likely_benign	0.1843	benign	-0.266	Destabilizing	0.002	N	0.254	neutral	N	0.501637541	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.