TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15870	47833;47834;47835	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
N2AB	14229	42910;42911;42912	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
N2A	13302	40129;40130;40131	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
N2B	6805	20638;20639;20640	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
Novex-1	6930	21013;21014;21015	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
Novex-2	6997	21214;21215;21216	chr2:178617477;178617476;178617475	chr2:179482204;179482203;179482202
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: Fn3-3
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.3939
• 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
D/H	None	None	0.931	D	0.667	0.307	0.275215494804	gnomAD-4.0.0	1.63927E-06	None	None	None	None	N	None	0	2.58345E-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
D/A	0.1657	likely_benign	0.1979	benign	-0.23	Destabilizing	0.201	N	0.585	neutral	N	0.478200815	None	None	N
D/C	0.5233	ambiguous	0.5631	ambiguous	0.195	Stabilizing	0.982	D	0.692	prob.neutral	None	None	None	None	N
D/E	0.1215	likely_benign	0.146	benign	-0.298	Destabilizing	0.002	N	0.161	neutral	N	0.458705987	None	None	N
D/F	0.4419	ambiguous	0.5081	ambiguous	-0.315	Destabilizing	0.982	D	0.703	prob.neutral	None	None	None	None	N
D/G	0.1689	likely_benign	0.1834	benign	-0.398	Destabilizing	0.334	N	0.576	neutral	N	0.5035633	None	None	N
D/H	0.2477	likely_benign	0.2769	benign	-0.184	Destabilizing	0.931	D	0.667	neutral	D	0.561869517	None	None	N
D/I	0.2728	likely_benign	0.3406	ambiguous	0.154	Stabilizing	0.826	D	0.737	prob.delet.	None	None	None	None	N
D/K	0.2759	likely_benign	0.3104	benign	0.495	Stabilizing	0.25	N	0.611	neutral	None	None	None	None	N
D/L	0.2574	likely_benign	0.3078	benign	0.154	Stabilizing	0.7	D	0.728	prob.delet.	None	None	None	None	N
D/M	0.5321	ambiguous	0.6071	pathogenic	0.337	Stabilizing	0.982	D	0.685	prob.neutral	None	None	None	None	N
D/N	0.0972	likely_benign	0.1126	benign	0.239	Stabilizing	0.004	N	0.217	neutral	N	0.476551679	None	None	N
D/P	0.6796	likely_pathogenic	0.7249	pathogenic	0.048	Stabilizing	0.826	D	0.701	prob.neutral	None	None	None	None	N
D/Q	0.256	likely_benign	0.2963	benign	0.242	Stabilizing	0.539	D	0.595	neutral	None	None	None	None	N
D/R	0.3227	likely_benign	0.361	ambiguous	0.55	Stabilizing	0.539	D	0.694	prob.neutral	None	None	None	None	N
D/S	0.1293	likely_benign	0.1483	benign	0.152	Stabilizing	0.25	N	0.473	neutral	None	None	None	None	N
D/T	0.2228	likely_benign	0.2692	benign	0.282	Stabilizing	0.7	D	0.653	neutral	None	None	None	None	N
D/V	0.1768	likely_benign	0.2208	benign	0.048	Stabilizing	0.638	D	0.726	prob.delet.	D	0.566644813	None	None	N
D/W	0.8071	likely_pathogenic	0.8304	pathogenic	-0.223	Destabilizing	0.982	D	0.675	neutral	None	None	None	None	N
D/Y	0.1903	likely_benign	0.2122	benign	-0.079	Destabilizing	0.976	D	0.706	prob.neutral	D	0.609631232	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.