TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14108	42547;42548;42549	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
N2AB	12467	37624;37625;37626	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
N2A	11540	34843;34844;34845	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
N2B	5043	15352;15353;15354	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
Novex-1	5168	15727;15728;15729	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
Novex-2	5235	15928;15929;15930	chr2:178634459;178634458;178634457	chr2:179499186;179499185;179499184
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-91
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.1553
• 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
I/F	rs772414514	-1.698	0.627	N	0.645	0.226	0.576639666579	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
I/F	rs772414514	-1.698	0.627	N	0.645	0.226	0.576639666579	gnomAD-4.0.0	6.15989E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.04367E-04	0
I/N	None	None	0.773	N	0.679	0.341	0.769439331453	gnomAD-4.0.0	6.84434E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99675E-07	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
I/A	0.8761	likely_pathogenic	0.7862	pathogenic	-3.012	Highly Destabilizing	0.116	N	0.571	neutral	None	None	None	None	N
I/C	0.9182	likely_pathogenic	0.8851	pathogenic	-2.171	Highly Destabilizing	0.981	D	0.646	neutral	None	None	None	None	N
I/D	0.9865	likely_pathogenic	0.9672	pathogenic	-3.619	Highly Destabilizing	0.818	D	0.679	prob.neutral	None	None	None	None	N
I/E	0.9541	likely_pathogenic	0.8966	pathogenic	-3.383	Highly Destabilizing	0.818	D	0.68	prob.neutral	None	None	None	None	N
I/F	0.4094	ambiguous	0.3191	benign	-1.779	Destabilizing	0.627	D	0.645	neutral	N	0.503649496	None	None	N
I/G	0.9725	likely_pathogenic	0.9484	pathogenic	-3.511	Highly Destabilizing	0.001	N	0.53	neutral	None	None	None	None	N
I/H	0.8882	likely_pathogenic	0.8162	pathogenic	-2.99	Highly Destabilizing	0.981	D	0.693	prob.neutral	None	None	None	None	N
I/K	0.9046	likely_pathogenic	0.8136	pathogenic	-2.437	Highly Destabilizing	0.388	N	0.677	prob.neutral	None	None	None	None	N
I/L	0.295	likely_benign	0.2288	benign	-1.524	Destabilizing	0.015	N	0.435	neutral	D	0.524870568	None	None	N
I/M	0.2054	likely_benign	0.1539	benign	-1.491	Destabilizing	0.006	N	0.287	neutral	N	0.489233319	None	None	N
I/N	0.8458	likely_pathogenic	0.7336	pathogenic	-2.849	Highly Destabilizing	0.773	D	0.679	prob.neutral	N	0.50896261	None	None	N
I/P	0.9985	likely_pathogenic	0.9976	pathogenic	-2.01	Highly Destabilizing	0.932	D	0.682	prob.neutral	None	None	None	None	N
I/Q	0.8714	likely_pathogenic	0.7841	pathogenic	-2.679	Highly Destabilizing	0.818	D	0.687	prob.neutral	None	None	None	None	N
I/R	0.8383	likely_pathogenic	0.7213	pathogenic	-2.082	Highly Destabilizing	0.69	D	0.681	prob.neutral	None	None	None	None	N
I/S	0.7989	likely_pathogenic	0.6538	pathogenic	-3.418	Highly Destabilizing	0.324	N	0.634	neutral	N	0.452208778	None	None	N
I/T	0.738	likely_pathogenic	0.5625	ambiguous	-3.066	Highly Destabilizing	0.324	N	0.636	neutral	N	0.465788835	None	None	N
I/V	0.178	likely_benign	0.1553	benign	-2.01	Highly Destabilizing	0.041	N	0.417	neutral	N	0.502171233	None	None	N
I/W	0.9418	likely_pathogenic	0.9151	pathogenic	-2.257	Highly Destabilizing	0.981	D	0.702	prob.neutral	None	None	None	None	N
I/Y	0.7466	likely_pathogenic	0.684	pathogenic	-2.081	Highly Destabilizing	0.818	D	0.67	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.