TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15971	48136;48137;48138	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
N2AB	14330	43213;43214;43215	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
N2A	13403	40432;40433;40434	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
N2B	6906	20941;20942;20943	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
Novex-1	7031	21316;21317;21318	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
Novex-2	7098	21517;21518;21519	chr2:178616978;178616977;178616976	chr2:179481705;179481704;179481703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-109
• Domain position: 4
• Structural Position: 11
• Q(SASA): 0.2681
• 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/V	None	None	1.0	D	0.783	0.508	0.59734385502	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	0.4434	ambiguous	0.3743	ambiguous	-0.348	Destabilizing	1.0	D	0.645	neutral	N	0.488066107	None	None	N
G/C	0.535	ambiguous	0.4861	ambiguous	-0.807	Destabilizing	1.0	D	0.761	deleterious	D	0.587842461	None	None	N
G/D	0.7473	likely_pathogenic	0.6754	pathogenic	-0.676	Destabilizing	1.0	D	0.745	deleterious	N	0.518001059	None	None	N
G/E	0.7565	likely_pathogenic	0.6747	pathogenic	-0.797	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
G/F	0.9285	likely_pathogenic	0.9121	pathogenic	-0.921	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
G/H	0.7835	likely_pathogenic	0.7242	pathogenic	-0.851	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/I	0.8124	likely_pathogenic	0.7633	pathogenic	-0.272	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
G/K	0.7862	likely_pathogenic	0.7094	pathogenic	-1.034	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
G/L	0.9054	likely_pathogenic	0.8842	pathogenic	-0.272	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/M	0.9021	likely_pathogenic	0.8773	pathogenic	-0.384	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
G/N	0.7305	likely_pathogenic	0.667	pathogenic	-0.614	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
G/P	0.9742	likely_pathogenic	0.964	pathogenic	-0.26	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
G/Q	0.7571	likely_pathogenic	0.6806	pathogenic	-0.829	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/R	0.6407	likely_pathogenic	0.5619	ambiguous	-0.675	Destabilizing	1.0	D	0.771	deleterious	D	0.541657077	None	None	N
G/S	0.3266	likely_benign	0.2758	benign	-0.772	Destabilizing	1.0	D	0.711	prob.delet.	D	0.54147907	None	None	N
G/T	0.5742	likely_pathogenic	0.4924	ambiguous	-0.814	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/V	0.7042	likely_pathogenic	0.6361	pathogenic	-0.26	Destabilizing	1.0	D	0.783	deleterious	D	0.585256968	None	None	N
G/W	0.8597	likely_pathogenic	0.8218	pathogenic	-1.185	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
G/Y	0.854	likely_pathogenic	0.8178	pathogenic	-0.797	Destabilizing	1.0	D	0.769	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.