TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26746	80461;80462;80463	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
N2AB	25105	75538;75539;75540	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
N2A	24178	72757;72758;72759	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
N2B	17681	53266;53267;53268	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
Novex-1	17806	53641;53642;53643	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
Novex-2	17873	53842;53843;53844	chr2:178565896;178565895;178565894	chr2:179430623;179430622;179430621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-82
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.9235
• 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
N/H	None	None	0.015	N	0.259	0.151	0.168933306366	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	7.32654E-05
N/K	rs1299776307	0.473	0.684	N	0.325	0.134	0.148003135375	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	2.28676E-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
N/A	0.2155	likely_benign	0.227	benign	-0.195	Destabilizing	0.543	D	0.345	neutral	None	None	None	None	N
N/C	0.2721	likely_benign	0.2768	benign	0.285	Stabilizing	0.996	D	0.4	neutral	None	None	None	None	N
N/D	0.1349	likely_benign	0.1263	benign	0.124	Stabilizing	0.003	N	0.146	neutral	N	0.423643056	None	None	N
N/E	0.3563	ambiguous	0.3528	ambiguous	0.072	Stabilizing	0.373	N	0.302	neutral	None	None	None	None	N
N/F	0.5138	ambiguous	0.4992	ambiguous	-0.695	Destabilizing	0.953	D	0.427	neutral	None	None	None	None	N
N/G	0.1848	likely_benign	0.2023	benign	-0.324	Destabilizing	0.001	N	0.119	neutral	None	None	None	None	N
N/H	0.128	likely_benign	0.1219	benign	-0.33	Destabilizing	0.015	N	0.259	neutral	N	0.474976409	None	None	N
N/I	0.3086	likely_benign	0.2976	benign	0.048	Stabilizing	0.939	D	0.439	neutral	N	0.512287782	None	None	N
N/K	0.3119	likely_benign	0.2826	benign	0.133	Stabilizing	0.684	D	0.325	neutral	N	0.469975566	None	None	N
N/L	0.291	likely_benign	0.2939	benign	0.048	Stabilizing	0.91	D	0.448	neutral	None	None	None	None	N
N/M	0.3074	likely_benign	0.311	benign	0.235	Stabilizing	0.996	D	0.381	neutral	None	None	None	None	N
N/P	0.6389	likely_pathogenic	0.6768	pathogenic	-0.008	Destabilizing	0.984	D	0.419	neutral	None	None	None	None	N
N/Q	0.3093	likely_benign	0.3087	benign	-0.251	Destabilizing	0.91	D	0.365	neutral	None	None	None	None	N
N/R	0.4237	ambiguous	0.406	ambiguous	0.213	Stabilizing	0.742	D	0.348	neutral	None	None	None	None	N
N/S	0.1118	likely_benign	0.1132	benign	-0.024	Destabilizing	0.472	N	0.339	neutral	N	0.505088217	None	None	N
N/T	0.1547	likely_benign	0.163	benign	0.05	Stabilizing	0.815	D	0.324	neutral	N	0.484940363	None	None	N
N/V	0.2956	likely_benign	0.303	benign	-0.008	Destabilizing	0.953	D	0.455	neutral	None	None	None	None	N
N/W	0.7564	likely_pathogenic	0.7468	pathogenic	-0.762	Destabilizing	0.996	D	0.472	neutral	None	None	None	None	N
N/Y	0.1746	likely_benign	0.1572	benign	-0.462	Destabilizing	0.792	D	0.418	neutral	N	0.489321682	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.