TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6206	18841;18842;18843	chr2:178729540;178729539;178729538	chr2:179594267;179594266;179594265
N2AB	5889	17890;17891;17892	chr2:178729540;178729539;178729538	chr2:179594267;179594266;179594265
N2A	4962	15109;15110;15111	chr2:178729540;178729539;178729538	chr2:179594267;179594266;179594265
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-46
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7128
• 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
K/N	None	None	0.055	N	0.277	0.139	0.170165803431	gnomAD-4.0.0	6.8456E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99857E-07	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
K/A	0.1871	likely_benign	0.2409	benign	0.036	Stabilizing	None	N	0.082	neutral	None	None	None	None	I
K/C	0.51	ambiguous	0.5821	pathogenic	-0.395	Destabilizing	0.628	D	0.296	neutral	None	None	None	None	I
K/D	0.3126	likely_benign	0.3998	ambiguous	-0.142	Destabilizing	0.016	N	0.307	neutral	None	None	None	None	I
K/E	0.0928	likely_benign	0.1121	benign	-0.126	Destabilizing	None	N	0.077	neutral	N	0.409847906	None	None	I
K/F	0.48	ambiguous	0.5638	ambiguous	-0.167	Destabilizing	0.214	N	0.368	neutral	None	None	None	None	I
K/G	0.2482	likely_benign	0.3047	benign	-0.147	Destabilizing	0.031	N	0.277	neutral	None	None	None	None	I
K/H	0.1806	likely_benign	0.2159	benign	-0.273	Destabilizing	0.356	N	0.283	neutral	None	None	None	None	I
K/I	0.1891	likely_benign	0.238	benign	0.443	Stabilizing	0.038	N	0.475	neutral	None	None	None	None	I
K/L	0.1653	likely_benign	0.2023	benign	0.443	Stabilizing	None	N	0.123	neutral	None	None	None	None	I
K/M	0.1415	likely_benign	0.161	benign	-0.022	Destabilizing	0.171	N	0.283	neutral	D	0.523712129	None	None	I
K/N	0.2032	likely_benign	0.2461	benign	0.007	Stabilizing	0.055	N	0.277	neutral	N	0.518631596	None	None	I
K/P	0.3992	ambiguous	0.5406	ambiguous	0.334	Stabilizing	None	N	0.135	neutral	None	None	None	None	I
K/Q	0.0824	likely_benign	0.0935	benign	-0.094	Destabilizing	0.029	N	0.307	neutral	N	0.452675963	None	None	I
K/R	0.0782	likely_benign	0.0869	benign	-0.099	Destabilizing	None	N	0.062	neutral	N	0.442632328	None	None	I
K/S	0.1982	likely_benign	0.2391	benign	-0.377	Destabilizing	0.001	N	0.085	neutral	None	None	None	None	I
K/T	0.1041	likely_benign	0.125	benign	-0.221	Destabilizing	0.012	N	0.28	neutral	N	0.479401205	None	None	I
K/V	0.1861	likely_benign	0.2327	benign	0.334	Stabilizing	0.016	N	0.322	neutral	None	None	None	None	I
K/W	0.534	ambiguous	0.5853	pathogenic	-0.255	Destabilizing	0.864	D	0.294	neutral	None	None	None	None	I
K/Y	0.3776	ambiguous	0.4361	ambiguous	0.097	Stabilizing	0.628	D	0.356	neutral	None	None	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.