TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22163	66712;66713;66714	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
N2AB	20522	61789;61790;61791	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
N2A	19595	59008;59009;59010	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
N2B	13098	39517;39518;39519	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
Novex-1	13223	39892;39893;39894	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
Novex-2	13290	40093;40094;40095	chr2:178581781;178581780;178581779	chr2:179446508;179446507;179446506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-49
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2349
• 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
P/L	rs752183879	0.077	0.976	N	0.806	0.368	0.462022758384	gnomAD-2.1.1	4.38E-06	None	None	None	None	N	None	0	3.21E-05	None	0	0	None	0	None	0	0	0
P/L	rs752183879	0.077	0.976	N	0.806	0.368	0.462022758384	gnomAD-4.0.0	6.5072E-06	None	None	None	None	N	None	5.8418E-05	4.83349E-05	None	0	0	None	0	0	2.91566E-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
P/A	0.6949	likely_pathogenic	0.74	pathogenic	-1.897	Destabilizing	0.958	D	0.739	prob.delet.	N	0.494993221	None	None	N
P/C	0.9412	likely_pathogenic	0.9566	pathogenic	-1.509	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.561	Highly Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
P/E	0.9977	likely_pathogenic	0.9985	pathogenic	-2.374	Highly Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
P/F	0.9948	likely_pathogenic	0.9956	pathogenic	-1.079	Destabilizing	0.334	N	0.662	neutral	None	None	None	None	N
P/G	0.9783	likely_pathogenic	0.9846	pathogenic	-2.397	Highly Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
P/H	0.9949	likely_pathogenic	0.9965	pathogenic	-2.264	Highly Destabilizing	0.999	D	0.843	deleterious	D	0.543571995	None	None	N
P/I	0.9031	likely_pathogenic	0.9248	pathogenic	-0.519	Destabilizing	0.982	D	0.849	deleterious	None	None	None	None	N
P/K	0.9981	likely_pathogenic	0.9987	pathogenic	-1.57	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
P/L	0.7608	likely_pathogenic	0.7987	pathogenic	-0.519	Destabilizing	0.976	D	0.806	deleterious	N	0.498305813	None	None	N
P/M	0.9673	likely_pathogenic	0.9728	pathogenic	-0.652	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
P/N	0.9981	likely_pathogenic	0.9987	pathogenic	-1.794	Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
P/Q	0.991	likely_pathogenic	0.994	pathogenic	-1.673	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
P/R	0.9927	likely_pathogenic	0.9953	pathogenic	-1.427	Destabilizing	0.998	D	0.855	deleterious	D	0.543571995	None	None	N
P/S	0.9646	likely_pathogenic	0.9748	pathogenic	-2.357	Highly Destabilizing	0.994	D	0.784	deleterious	D	0.531797616	None	None	N
P/T	0.9207	likely_pathogenic	0.9382	pathogenic	-2.04	Highly Destabilizing	0.994	D	0.796	deleterious	D	0.543065016	None	None	N
P/V	0.7778	likely_pathogenic	0.8243	pathogenic	-0.95	Destabilizing	0.991	D	0.81	deleterious	None	None	None	None	N
P/W	0.9987	likely_pathogenic	0.9991	pathogenic	-1.621	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/Y	0.9981	likely_pathogenic	0.9988	pathogenic	-1.238	Destabilizing	0.982	D	0.848	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.