TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32773	98542;98543;98544	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
N2AB	31132	93619;93620;93621	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
N2A	30205	90838;90839;90840	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
N2B	23708	71347;71348;71349	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
Novex-1	23833	71722;71723;71724	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
Novex-2	23900	71923;71924;71925	chr2:178539748;178539747;178539746	chr2:179404475;179404474;179404473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-155
• Domain position: 66
• Structural Position: 154
• Q(SASA): 0.206
• 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/C	rs1693456839	None	1.0	D	0.818	0.72	0.787935859653	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs1693456839	None	1.0	D	0.818	0.72	0.787935859653	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	2.41336E-05	0	None	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	0.9975	likely_pathogenic	0.9975	pathogenic	-2.263	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/C	0.9502	likely_pathogenic	0.9467	pathogenic	-1.753	Destabilizing	1.0	D	0.818	deleterious	D	0.62718879	None	None	N
Y/D	0.9987	likely_pathogenic	0.9989	pathogenic	-2.978	Highly Destabilizing	1.0	D	0.859	deleterious	D	0.62718879	None	None	N
Y/E	0.9995	likely_pathogenic	0.9995	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/F	0.2212	likely_benign	0.1747	benign	-0.909	Destabilizing	0.999	D	0.697	prob.neutral	D	0.579696836	None	None	N
Y/G	0.9959	likely_pathogenic	0.9963	pathogenic	-2.711	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/H	0.9842	likely_pathogenic	0.9827	pathogenic	-2.335	Highly Destabilizing	1.0	D	0.779	deleterious	D	0.626986986	None	None	N
Y/I	0.9631	likely_pathogenic	0.963	pathogenic	-0.771	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9993	pathogenic	-1.9	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/L	0.9296	likely_pathogenic	0.9353	pathogenic	-0.771	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
Y/M	0.9842	likely_pathogenic	0.9826	pathogenic	-0.968	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/N	0.9945	likely_pathogenic	0.9947	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.62718879	None	None	N
Y/P	0.9991	likely_pathogenic	0.9993	pathogenic	-1.285	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/Q	0.9993	likely_pathogenic	0.9993	pathogenic	-2.34	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
Y/R	0.9963	likely_pathogenic	0.9964	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/S	0.9945	likely_pathogenic	0.9947	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.62718879	None	None	N
Y/T	0.9974	likely_pathogenic	0.9976	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/V	0.9415	likely_pathogenic	0.9414	pathogenic	-1.285	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
Y/W	0.7167	likely_pathogenic	0.6932	pathogenic	-0.334	Destabilizing	1.0	D	0.772	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.