TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22126	66601;66602;66603	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
N2AB	20485	61678;61679;61680	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
N2A	19558	58897;58898;58899	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
N2B	13061	39406;39407;39408	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
Novex-1	13186	39781;39782;39783	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
Novex-2	13253	39982;39983;39984	chr2:178581993;178581992;178581991	chr2:179446720;179446719;179446718
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: Fn3-48
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1184
• 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	rs1447894010	-2.042	1.0	D	0.832	0.848	0.730590183365	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/H	rs1447894010	-2.042	1.0	D	0.832	0.848	0.730590183365	gnomAD-4.0.0	8.21273E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.04275E-03	4.49835E-06	0	1.65717E-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
Y/A	0.9865	likely_pathogenic	0.9895	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/C	0.8534	likely_pathogenic	0.8867	pathogenic	-1.887	Destabilizing	1.0	D	0.811	deleterious	D	0.66620312	None	None	N
Y/D	0.9924	likely_pathogenic	0.9934	pathogenic	-3.348	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.682222481	None	None	N
Y/E	0.9963	likely_pathogenic	0.9972	pathogenic	-3.173	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/F	0.283	likely_benign	0.3185	benign	-1.138	Destabilizing	0.999	D	0.78	deleterious	D	0.619114774	None	None	N
Y/G	0.9802	likely_pathogenic	0.9834	pathogenic	-3.596	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/H	0.9662	likely_pathogenic	0.9723	pathogenic	-1.998	Destabilizing	1.0	D	0.832	deleterious	D	0.66620312	None	None	N
Y/I	0.9107	likely_pathogenic	0.9209	pathogenic	-1.883	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/K	0.9967	likely_pathogenic	0.9972	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/L	0.9147	likely_pathogenic	0.9278	pathogenic	-1.883	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
Y/M	0.9383	likely_pathogenic	0.9555	pathogenic	-1.597	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/N	0.9361	likely_pathogenic	0.9456	pathogenic	-2.866	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.666001315	None	None	N
Y/P	0.9994	likely_pathogenic	0.9995	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/Q	0.994	likely_pathogenic	0.996	pathogenic	-2.701	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/R	0.9922	likely_pathogenic	0.9929	pathogenic	-1.785	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/S	0.9748	likely_pathogenic	0.9798	pathogenic	-3.253	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.682222481	None	None	N
Y/T	0.9803	likely_pathogenic	0.9834	pathogenic	-2.968	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/V	0.8266	likely_pathogenic	0.8414	pathogenic	-2.334	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/W	0.8507	likely_pathogenic	0.8614	pathogenic	-0.477	Destabilizing	1.0	D	0.809	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.