TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8138	24637;24638;24639	chr2:178718788;178718787;178718786	chr2:179583515;179583514;179583513
N2AB	7821	23686;23687;23688	chr2:178718788;178718787;178718786	chr2:179583515;179583514;179583513
N2A	6894	20905;20906;20907	chr2:178718788;178718787;178718786	chr2:179583515;179583514;179583513
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-66
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3966
• 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
F/S	None	None	0.055	N	0.391	0.069	0.464442853059	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31868E-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
F/A	0.1832	likely_benign	0.1892	benign	-1.649	Destabilizing	0.031	N	0.323	neutral	None	None	None	None	N
F/C	0.2151	likely_benign	0.1906	benign	-0.506	Destabilizing	0.828	D	0.366	neutral	N	0.497467162	None	None	N
F/D	0.3479	ambiguous	0.3662	ambiguous	0.146	Stabilizing	0.038	N	0.447	neutral	None	None	None	None	N
F/E	0.3875	ambiguous	0.4062	ambiguous	0.156	Stabilizing	0.001	N	0.26	neutral	None	None	None	None	N
F/G	0.3488	ambiguous	0.3506	ambiguous	-1.911	Destabilizing	0.072	N	0.449	neutral	None	None	None	None	N
F/H	0.2107	likely_benign	0.2039	benign	-0.422	Destabilizing	0.001	N	0.219	neutral	None	None	None	None	N
F/I	0.1192	likely_benign	0.1266	benign	-0.918	Destabilizing	None	N	0.129	neutral	N	0.480417138	None	None	N
F/K	0.337	likely_benign	0.337	benign	-0.346	Destabilizing	0.072	N	0.442	neutral	None	None	None	None	N
F/L	0.3729	ambiguous	0.3709	ambiguous	-0.918	Destabilizing	None	N	0.096	neutral	N	0.435914212	None	None	N
F/M	0.2644	likely_benign	0.2533	benign	-0.567	Destabilizing	0.12	N	0.313	neutral	None	None	None	None	N
F/N	0.2401	likely_benign	0.2436	benign	-0.126	Destabilizing	0.038	N	0.453	neutral	None	None	None	None	N
F/P	0.5617	ambiguous	0.6154	pathogenic	-1.147	Destabilizing	0.356	N	0.445	neutral	None	None	None	None	N
F/Q	0.2982	likely_benign	0.2944	benign	-0.301	Destabilizing	0.214	N	0.465	neutral	None	None	None	None	N
F/R	0.2235	likely_benign	0.2276	benign	0.262	Stabilizing	0.214	N	0.467	neutral	None	None	None	None	N
F/S	0.1214	likely_benign	0.1252	benign	-0.958	Destabilizing	0.055	N	0.391	neutral	N	0.457076131	None	None	N
F/T	0.16	likely_benign	0.1679	benign	-0.858	Destabilizing	0.072	N	0.426	neutral	None	None	None	None	N
F/V	0.1235	likely_benign	0.1267	benign	-1.147	Destabilizing	0.004	N	0.331	neutral	N	0.49882954	None	None	N
F/W	0.2282	likely_benign	0.2229	benign	-0.527	Destabilizing	0.356	N	0.35	neutral	None	None	None	None	N
F/Y	0.0937	likely_benign	0.0905	benign	-0.525	Destabilizing	None	N	0.063	neutral	N	0.441282747	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.