TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14694	44305;44306;44307	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
N2AB	13053	39382;39383;39384	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
N2A	12126	36601;36602;36603	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
N2B	5629	17110;17111;17112	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
Novex-1	5754	17485;17486;17487	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
Novex-2	5821	17686;17687;17688	chr2:178630878;178630877;178630876	chr2:179495605;179495604;179495603
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-98
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.108
• 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
F/L	None	None	0.997	N	0.595	0.508	0.144782658237	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02682E-05

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
F/A	0.9984	likely_pathogenic	0.9963	pathogenic	-2.497	Highly Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
F/C	0.9925	likely_pathogenic	0.9868	pathogenic	-1.585	Destabilizing	1.0	D	0.811	deleterious	D	0.621382681	None	None	N
F/D	0.9998	likely_pathogenic	0.9995	pathogenic	-3.044	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
F/E	0.9997	likely_pathogenic	0.9992	pathogenic	-2.8	Highly Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
F/G	0.9992	likely_pathogenic	0.9979	pathogenic	-2.971	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
F/H	0.9986	likely_pathogenic	0.9967	pathogenic	-1.705	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
F/I	0.9353	likely_pathogenic	0.9009	pathogenic	-0.952	Destabilizing	0.999	D	0.633	neutral	D	0.608575818	None	None	N
F/K	0.9997	likely_pathogenic	0.9992	pathogenic	-2.135	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
F/L	0.9891	likely_pathogenic	0.9848	pathogenic	-0.952	Destabilizing	0.997	D	0.595	neutral	N	0.472160497	None	None	N
F/M	0.9729	likely_pathogenic	0.9606	pathogenic	-0.711	Destabilizing	1.0	D	0.731	deleterious	None	None	None	None	N
F/N	0.9996	likely_pathogenic	0.9987	pathogenic	-2.753	Highly Destabilizing	0.999	D	0.894	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	0.9999	pathogenic	-1.48	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
F/Q	0.9995	likely_pathogenic	0.9989	pathogenic	-2.564	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
F/R	0.999	likely_pathogenic	0.9976	pathogenic	-1.902	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	N
F/S	0.9993	likely_pathogenic	0.9977	pathogenic	-3.326	Highly Destabilizing	0.999	D	0.85	deleterious	D	0.621382681	None	None	N
F/T	0.999	likely_pathogenic	0.9973	pathogenic	-2.957	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
F/V	0.962	likely_pathogenic	0.9387	pathogenic	-1.48	Destabilizing	0.999	D	0.687	prob.delet.	D	0.614929036	None	None	N
F/W	0.9714	likely_pathogenic	0.955	pathogenic	-0.076	Destabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	N
F/Y	0.8982	likely_pathogenic	0.8446	pathogenic	-0.489	Destabilizing	0.997	D	0.581	neutral	D	0.619745637	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.