TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15424	46495;46496;46497	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
N2AB	13783	41572;41573;41574	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
N2A	12856	38791;38792;38793	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
N2B	6359	19300;19301;19302	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
Novex-1	6484	19675;19676;19677	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
Novex-2	6551	19876;19877;19878	chr2:178620251;178620250;178620249	chr2:179484978;179484977;179484976
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-106
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.2086
• 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
Y/H	rs1221444659	None	1.0	D	0.725	0.694	0.746174087732	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	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
Y/A	0.9496	likely_pathogenic	0.97	pathogenic	-2.789	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
Y/C	0.6121	likely_pathogenic	0.7029	pathogenic	-1.216	Destabilizing	1.0	D	0.765	deleterious	D	0.641881765	None	None	N
Y/D	0.9405	likely_pathogenic	0.9571	pathogenic	-1.655	Destabilizing	1.0	D	0.797	deleterious	D	0.717272459	None	None	N
Y/E	0.952	likely_pathogenic	0.9697	pathogenic	-1.544	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
Y/F	0.0899	likely_benign	0.1018	benign	-1.181	Destabilizing	0.999	D	0.541	neutral	D	0.536964644	None	None	N
Y/G	0.9208	likely_pathogenic	0.947	pathogenic	-3.128	Highly Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
Y/H	0.5148	ambiguous	0.6194	pathogenic	-1.384	Destabilizing	1.0	D	0.725	prob.delet.	D	0.629805502	None	None	N
Y/I	0.8116	likely_pathogenic	0.8426	pathogenic	-1.722	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
Y/K	0.9391	likely_pathogenic	0.9409	pathogenic	-1.429	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
Y/L	0.7171	likely_pathogenic	0.7732	pathogenic	-1.722	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
Y/M	0.7884	likely_pathogenic	0.8463	pathogenic	-1.298	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
Y/N	0.7022	likely_pathogenic	0.7725	pathogenic	-1.753	Destabilizing	1.0	D	0.773	deleterious	D	0.717534432	None	None	N
Y/P	0.999	likely_pathogenic	0.9991	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
Y/Q	0.8851	likely_pathogenic	0.9251	pathogenic	-1.719	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
Y/R	0.8881	likely_pathogenic	0.9026	pathogenic	-0.894	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
Y/S	0.7505	likely_pathogenic	0.8482	pathogenic	-2.321	Highly Destabilizing	1.0	D	0.753	deleterious	D	0.583418468	None	None	N
Y/T	0.8741	likely_pathogenic	0.9351	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
Y/V	0.7749	likely_pathogenic	0.8181	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
Y/W	0.5398	ambiguous	0.6143	pathogenic	-0.601	Destabilizing	1.0	D	0.704	prob.neutral	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.