TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29948	90067;90068;90069	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
N2AB	28307	85144;85145;85146	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
N2A	27380	82363;82364;82365	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
N2B	20883	62872;62873;62874	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
Novex-1	21008	63247;63248;63249	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
Novex-2	21075	63448;63449;63450	chr2:178553058;178553057;178553056	chr2:179417785;179417784;179417783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-106
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.1442
• 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
G/S	None	None	1.0	N	0.769	0.485	0.298056030225	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

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
G/A	0.3896	ambiguous	0.345	ambiguous	-0.706	Destabilizing	1.0	D	0.676	prob.neutral	N	0.475517458	None	None	N
G/C	0.5498	ambiguous	0.5323	ambiguous	-1.086	Destabilizing	1.0	D	0.699	prob.neutral	N	0.519577667	None	None	N
G/D	0.4341	ambiguous	0.3981	ambiguous	-1.263	Destabilizing	1.0	D	0.841	deleterious	N	0.344587627	None	None	N
G/E	0.5133	ambiguous	0.4586	ambiguous	-1.379	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/F	0.8967	likely_pathogenic	0.8806	pathogenic	-1.329	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/H	0.7318	likely_pathogenic	0.6954	pathogenic	-1.051	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/I	0.8619	likely_pathogenic	0.8433	pathogenic	-0.606	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/K	0.7836	likely_pathogenic	0.7407	pathogenic	-1.054	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/L	0.8584	likely_pathogenic	0.8313	pathogenic	-0.606	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/M	0.8404	likely_pathogenic	0.8201	pathogenic	-0.479	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
G/N	0.4261	ambiguous	0.3903	ambiguous	-0.767	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/P	0.9821	likely_pathogenic	0.9752	pathogenic	-0.604	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/Q	0.6426	likely_pathogenic	0.5986	pathogenic	-1.087	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/R	0.6923	likely_pathogenic	0.6584	pathogenic	-0.646	Destabilizing	1.0	D	0.811	deleterious	N	0.434420197	None	None	N
G/S	0.216	likely_benign	0.1945	benign	-0.961	Destabilizing	1.0	D	0.769	deleterious	N	0.391762711	None	None	N
G/T	0.4711	ambiguous	0.4307	ambiguous	-1.015	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/V	0.7586	likely_pathogenic	0.7336	pathogenic	-0.604	Destabilizing	1.0	D	0.808	deleterious	N	0.500471831	None	None	N
G/W	0.8007	likely_pathogenic	0.7873	pathogenic	-1.513	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
G/Y	0.7888	likely_pathogenic	0.7597	pathogenic	-1.143	Destabilizing	1.0	D	0.76	deleterious	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.