TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17642	53149;53150;53151	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
N2AB	16001	48226;48227;48228	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
N2A	15074	45445;45446;45447	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
N2B	8577	25954;25955;25956	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
Novex-1	8702	26329;26330;26331	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
Novex-2	8769	26530;26531;26532	chr2:178607863;178607862;178607861	chr2:179472590;179472589;179472588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-16
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1757
• 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
L/F	None	None	0.968	N	0.767	0.253	0.478905595755	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
L/A	0.9299	likely_pathogenic	0.9373	pathogenic	-2.618	Highly Destabilizing	0.825	D	0.756	deleterious	None	None	None	None	N
L/C	0.8505	likely_pathogenic	0.881	pathogenic	-1.789	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9991	pathogenic	-3.063	Highly Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
L/E	0.9948	likely_pathogenic	0.9948	pathogenic	-2.743	Highly Destabilizing	0.996	D	0.854	deleterious	None	None	None	None	N
L/F	0.2814	likely_benign	0.2592	benign	-1.5	Destabilizing	0.968	D	0.767	deleterious	N	0.354628475	None	None	N
L/G	0.9848	likely_pathogenic	0.9851	pathogenic	-3.25	Highly Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
L/H	0.983	likely_pathogenic	0.9849	pathogenic	-2.838	Highly Destabilizing	0.999	D	0.838	deleterious	N	0.501186694	None	None	N
L/I	0.1245	likely_benign	0.1324	benign	-0.735	Destabilizing	0.011	N	0.285	neutral	N	0.415314362	None	None	N
L/K	0.9929	likely_pathogenic	0.9935	pathogenic	-2.003	Highly Destabilizing	0.988	D	0.827	deleterious	None	None	None	None	N
L/M	0.2592	likely_benign	0.2624	benign	-0.775	Destabilizing	0.976	D	0.754	deleterious	None	None	None	None	N
L/N	0.9938	likely_pathogenic	0.9948	pathogenic	-2.639	Highly Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	N
L/P	0.9838	likely_pathogenic	0.987	pathogenic	-1.35	Destabilizing	0.995	D	0.852	deleterious	N	0.519945813	None	None	N
L/Q	0.9825	likely_pathogenic	0.984	pathogenic	-2.303	Highly Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
L/R	0.9837	likely_pathogenic	0.984	pathogenic	-2.024	Highly Destabilizing	0.995	D	0.828	deleterious	N	0.519772455	None	None	N
L/S	0.9908	likely_pathogenic	0.9918	pathogenic	-3.309	Highly Destabilizing	0.988	D	0.809	deleterious	None	None	None	None	N
L/T	0.958	likely_pathogenic	0.9643	pathogenic	-2.815	Highly Destabilizing	0.919	D	0.771	deleterious	None	None	None	None	N
L/V	0.1655	likely_benign	0.1743	benign	-1.35	Destabilizing	0.046	N	0.309	neutral	N	0.40238235	None	None	N
L/W	0.8835	likely_pathogenic	0.8859	pathogenic	-1.91	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
L/Y	0.8857	likely_pathogenic	0.8816	pathogenic	-1.632	Destabilizing	0.996	D	0.757	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.