TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17613	53062;53063;53064	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
N2AB	15972	48139;48140;48141	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
N2A	15045	45358;45359;45360	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
N2B	8548	25867;25868;25869	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
Novex-1	8673	26242;26243;26244	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
Novex-2	8740	26443;26444;26445	chr2:178607950;178607949;178607948	chr2:179472677;179472676;179472675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-16
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2858
• 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
T/I	None	None	0.885	N	0.313	0.328	0.303453137403	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	None	None	0.17	N	0.3	0.088	0.0762999501168	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-06	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
T/A	0.105	likely_benign	0.0935	benign	-0.357	Destabilizing	0.76	D	0.347	neutral	N	0.487088741	None	None	N
T/C	0.4854	ambiguous	0.4178	ambiguous	-0.259	Destabilizing	0.999	D	0.423	neutral	None	None	None	None	N
T/D	0.3891	ambiguous	0.325	benign	0.13	Stabilizing	0.986	D	0.353	neutral	None	None	None	None	N
T/E	0.2836	likely_benign	0.2371	benign	0.05	Stabilizing	0.986	D	0.339	neutral	None	None	None	None	N
T/F	0.4137	ambiguous	0.3227	benign	-0.851	Destabilizing	0.993	D	0.517	neutral	None	None	None	None	N
T/G	0.2482	likely_benign	0.2194	benign	-0.481	Destabilizing	0.91	D	0.389	neutral	None	None	None	None	N
T/H	0.3526	ambiguous	0.3023	benign	-0.787	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	N
T/I	0.2853	likely_benign	0.2087	benign	-0.149	Destabilizing	0.885	D	0.313	neutral	N	0.468733941	None	None	N
T/K	0.1954	likely_benign	0.1623	benign	-0.383	Destabilizing	0.982	D	0.34	neutral	N	0.490225047	None	None	N
T/L	0.1614	likely_benign	0.1326	benign	-0.149	Destabilizing	0.91	D	0.312	neutral	None	None	None	None	N
T/M	0.1252	likely_benign	0.1016	benign	0.034	Stabilizing	0.998	D	0.377	neutral	None	None	None	None	N
T/N	0.1398	likely_benign	0.1198	benign	-0.142	Destabilizing	0.986	D	0.328	neutral	None	None	None	None	N
T/P	0.4485	ambiguous	0.3606	ambiguous	-0.19	Destabilizing	0.991	D	0.365	neutral	N	0.467466493	None	None	N
T/Q	0.2216	likely_benign	0.1934	benign	-0.386	Destabilizing	0.993	D	0.351	neutral	None	None	None	None	N
T/R	0.1966	likely_benign	0.1583	benign	-0.1	Destabilizing	0.982	D	0.351	neutral	N	0.513389908	None	None	N
T/S	0.1169	likely_benign	0.1103	benign	-0.35	Destabilizing	0.17	N	0.3	neutral	N	0.44839428	None	None	N
T/V	0.1961	likely_benign	0.1617	benign	-0.19	Destabilizing	0.06	N	0.292	neutral	None	None	None	None	N
T/W	0.6751	likely_pathogenic	0.5699	pathogenic	-0.854	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
T/Y	0.4197	ambiguous	0.3429	ambiguous	-0.576	Destabilizing	0.998	D	0.513	neutral	None	None	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.