TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30292	91099;91100;91101	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
N2AB	28651	86176;86177;86178	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
N2A	27724	83395;83396;83397	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
N2B	21227	63904;63905;63906	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
Novex-1	21352	64279;64280;64281	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
Novex-2	21419	64480;64481;64482	chr2:178552026;178552025;178552024	chr2:179416753;179416752;179416751
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: Fn3-108
• Domain position: 69
• Structural Position: 100
• Q(SASA): 1.0034
• 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/N	None	None	0.896	N	0.576	0.261	0.210429274316	gnomAD-4.0.0	1.5922E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43394E-05	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	0.3359	likely_benign	0.2618	benign	-0.219	Destabilizing	0.811	D	0.651	neutral	N	0.466705974	None	None	I
D/C	0.7473	likely_pathogenic	0.6819	pathogenic	-0.051	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
D/E	0.1928	likely_benign	0.1798	benign	-0.304	Destabilizing	0.946	D	0.479	neutral	N	0.484483658	None	None	I
D/F	0.6895	likely_pathogenic	0.6347	pathogenic	-0.18	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	I
D/G	0.1266	likely_benign	0.0997	benign	-0.41	Destabilizing	0.004	N	0.376	neutral	N	0.310277478	None	None	I
D/H	0.4179	ambiguous	0.3605	ambiguous	0.042	Stabilizing	0.999	D	0.591	neutral	N	0.477037611	None	None	I
D/I	0.7176	likely_pathogenic	0.6337	pathogenic	0.233	Stabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	I
D/K	0.6522	likely_pathogenic	0.5665	pathogenic	0.211	Stabilizing	0.988	D	0.584	neutral	None	None	None	None	I
D/L	0.6034	likely_pathogenic	0.5362	ambiguous	0.233	Stabilizing	0.988	D	0.701	prob.neutral	None	None	None	None	I
D/M	0.7581	likely_pathogenic	0.703	pathogenic	0.268	Stabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
D/N	0.1168	likely_benign	0.1043	benign	-0.01	Destabilizing	0.896	D	0.576	neutral	N	0.43547899	None	None	I
D/P	0.9486	likely_pathogenic	0.9224	pathogenic	0.104	Stabilizing	0.996	D	0.599	neutral	None	None	None	None	I
D/Q	0.5282	ambiguous	0.4752	ambiguous	0.012	Stabilizing	0.996	D	0.527	neutral	None	None	None	None	I
D/R	0.6869	likely_pathogenic	0.6039	pathogenic	0.43	Stabilizing	0.988	D	0.693	prob.neutral	None	None	None	None	I
D/S	0.2094	likely_benign	0.1677	benign	-0.143	Destabilizing	0.919	D	0.537	neutral	None	None	None	None	I
D/T	0.4388	ambiguous	0.3707	ambiguous	-0.001	Destabilizing	0.988	D	0.581	neutral	None	None	None	None	I
D/V	0.5025	ambiguous	0.4227	ambiguous	0.104	Stabilizing	0.984	D	0.693	prob.neutral	N	0.473383474	None	None	I
D/W	0.9056	likely_pathogenic	0.8761	pathogenic	-0.075	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
D/Y	0.2676	likely_benign	0.2294	benign	0.047	Stabilizing	0.995	D	0.717	prob.delet.	N	0.475768175	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.