TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20173	60742;60743;60744	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
N2AB	18532	55819;55820;55821	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
N2A	17605	53038;53039;53040	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
N2B	11108	33547;33548;33549	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
Novex-1	11233	33922;33923;33924	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
Novex-2	11300	34123;34124;34125	chr2:178591208;178591207;178591206	chr2:179455935;179455934;179455933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-34
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2014
• 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/R	None	None	0.999	N	0.808	0.381	0.566883017009	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
G/A	0.3062	likely_benign	0.3597	ambiguous	-0.862	Destabilizing	0.406	N	0.389	neutral	N	0.484328943	None	None	N
G/C	0.6309	likely_pathogenic	0.6968	pathogenic	-1.232	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/D	0.7293	likely_pathogenic	0.7673	pathogenic	-2.092	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
G/E	0.7963	likely_pathogenic	0.8325	pathogenic	-2.143	Highly Destabilizing	0.999	D	0.787	deleterious	N	0.490736806	None	None	N
G/F	0.9254	likely_pathogenic	0.9444	pathogenic	-1.247	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
G/H	0.9066	likely_pathogenic	0.9322	pathogenic	-1.389	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/I	0.895	likely_pathogenic	0.9293	pathogenic	-0.499	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
G/K	0.9346	likely_pathogenic	0.9502	pathogenic	-1.373	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
G/L	0.8099	likely_pathogenic	0.846	pathogenic	-0.499	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
G/M	0.8818	likely_pathogenic	0.9124	pathogenic	-0.444	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
G/N	0.7607	likely_pathogenic	0.7945	pathogenic	-1.197	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/P	0.9895	likely_pathogenic	0.9917	pathogenic	-0.582	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
G/Q	0.8593	likely_pathogenic	0.8924	pathogenic	-1.441	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/R	0.8899	likely_pathogenic	0.9185	pathogenic	-1.018	Destabilizing	0.999	D	0.808	deleterious	N	0.492257743	None	None	N
G/S	0.1919	likely_benign	0.2281	benign	-1.357	Destabilizing	0.988	D	0.662	neutral	None	None	None	None	N
G/T	0.5649	likely_pathogenic	0.6429	pathogenic	-1.349	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
G/V	0.819	likely_pathogenic	0.8728	pathogenic	-0.582	Destabilizing	0.998	D	0.775	deleterious	N	0.504628007	None	None	N
G/W	0.9224	likely_pathogenic	0.9421	pathogenic	-1.598	Destabilizing	1.0	D	0.795	deleterious	N	0.504881496	None	None	N
G/Y	0.8927	likely_pathogenic	0.9213	pathogenic	-1.199	Destabilizing	1.0	D	0.838	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.