TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5670	17233;17234;17235	chr2:178731867;178731866;178731865	chr2:179596594;179596593;179596592
N2AB	5353	16282;16283;16284	chr2:178731867;178731866;178731865	chr2:179596594;179596593;179596592
N2A	4426	13501;13502;13503	chr2:178731867;178731866;178731865	chr2:179596594;179596593;179596592
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-40
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1329
• 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
W/C	rs759141317	-1.498	0.077	D	0.701	0.624	0.877831071711	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
W/C	rs759141317	-1.498	0.077	D	0.701	0.624	0.877831071711	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8585E-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
W/A	0.9558	likely_pathogenic	0.941	pathogenic	-2.484	Highly Destabilizing	0.939	D	0.807	deleterious	None	None	None	None	N
W/C	0.9499	likely_pathogenic	0.9296	pathogenic	-1.15	Destabilizing	0.077	N	0.701	prob.neutral	D	0.65756118	None	None	N
W/D	0.9992	likely_pathogenic	0.9988	pathogenic	-2.969	Highly Destabilizing	0.997	D	0.856	deleterious	None	None	None	None	N
W/E	0.9989	likely_pathogenic	0.9986	pathogenic	-2.837	Highly Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
W/F	0.3812	ambiguous	0.3426	ambiguous	-1.4	Destabilizing	0.046	N	0.495	neutral	None	None	None	None	N
W/G	0.939	likely_pathogenic	0.9126	pathogenic	-2.735	Highly Destabilizing	0.959	D	0.795	deleterious	D	0.689630263	None	None	N
W/H	0.9906	likely_pathogenic	0.9897	pathogenic	-1.89	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
W/I	0.8503	likely_pathogenic	0.8339	pathogenic	-1.543	Destabilizing	0.884	D	0.824	deleterious	None	None	None	None	N
W/K	0.9994	likely_pathogenic	0.9993	pathogenic	-1.99	Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
W/L	0.7289	likely_pathogenic	0.7135	pathogenic	-1.543	Destabilizing	0.035	N	0.622	neutral	D	0.647840625	None	None	N
W/M	0.9253	likely_pathogenic	0.909	pathogenic	-1.062	Destabilizing	0.982	D	0.787	deleterious	None	None	None	None	N
W/N	0.9973	likely_pathogenic	0.9964	pathogenic	-2.745	Highly Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
W/P	0.9961	likely_pathogenic	0.9949	pathogenic	-1.884	Destabilizing	0.997	D	0.848	deleterious	None	None	None	None	N
W/Q	0.9984	likely_pathogenic	0.998	pathogenic	-2.512	Highly Destabilizing	0.997	D	0.823	deleterious	None	None	None	None	N
W/R	0.9977	likely_pathogenic	0.9972	pathogenic	-1.968	Destabilizing	0.996	D	0.857	deleterious	D	0.689832067	None	None	N
W/S	0.9587	likely_pathogenic	0.9452	pathogenic	-2.853	Highly Destabilizing	0.988	D	0.833	deleterious	D	0.689832067	None	None	N
W/T	0.9691	likely_pathogenic	0.9586	pathogenic	-2.642	Highly Destabilizing	0.969	D	0.803	deleterious	None	None	None	None	N
W/V	0.8132	likely_pathogenic	0.7858	pathogenic	-1.884	Destabilizing	0.884	D	0.814	deleterious	None	None	None	None	N
W/Y	0.7855	likely_pathogenic	0.7703	pathogenic	-1.201	Destabilizing	0.884	D	0.715	prob.delet.	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.