TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16610	50053;50054;50055	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
N2AB	14969	45130;45131;45132	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
N2A	14042	42349;42350;42351	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
N2B	7545	22858;22859;22860	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
Novex-1	7670	23233;23234;23235	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
Novex-2	7737	23434;23435;23436	chr2:178612893;178612892;178612891	chr2:179477620;179477619;179477618
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-8
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.2047
• 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
H/Q	None	None	0.999	N	0.479	0.348	0.181679512989	gnomAD-4.0.0	3.18759E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	4.83793E-04	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
H/A	0.618	likely_pathogenic	0.5679	pathogenic	-1.784	Destabilizing	0.993	D	0.533	neutral	None	None	None	None	N
H/C	0.2693	likely_benign	0.2123	benign	-0.868	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
H/D	0.7955	likely_pathogenic	0.8008	pathogenic	-1.838	Destabilizing	0.999	D	0.564	neutral	D	0.557076379	None	None	N
H/E	0.7189	likely_pathogenic	0.7106	pathogenic	-1.653	Destabilizing	0.998	D	0.417	neutral	None	None	None	None	N
H/F	0.3199	likely_benign	0.2438	benign	0.099	Stabilizing	0.991	D	0.568	neutral	None	None	None	None	N
H/G	0.7495	likely_pathogenic	0.7417	pathogenic	-2.208	Highly Destabilizing	0.998	D	0.576	neutral	None	None	None	None	N
H/I	0.5382	ambiguous	0.4709	ambiguous	-0.53	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
H/K	0.6715	likely_pathogenic	0.69	pathogenic	-1.221	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	N
H/L	0.2566	likely_benign	0.2262	benign	-0.53	Destabilizing	0.98	D	0.653	neutral	N	0.464468271	None	None	N
H/M	0.6673	likely_pathogenic	0.6197	pathogenic	-0.687	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
H/N	0.3711	ambiguous	0.3324	benign	-1.91	Destabilizing	0.997	D	0.457	neutral	N	0.514743532	None	None	N
H/P	0.8971	likely_pathogenic	0.9047	pathogenic	-0.937	Destabilizing	0.999	D	0.707	prob.neutral	D	0.597544745	None	None	N
H/Q	0.482	ambiguous	0.4509	ambiguous	-1.572	Destabilizing	0.999	D	0.479	neutral	N	0.464823851	None	None	N
H/R	0.4002	ambiguous	0.4085	ambiguous	-1.546	Destabilizing	0.999	D	0.465	neutral	N	0.513937609	None	None	N
H/S	0.5964	likely_pathogenic	0.5561	ambiguous	-1.944	Destabilizing	0.993	D	0.533	neutral	None	None	None	None	N
H/T	0.618	likely_pathogenic	0.5816	pathogenic	-1.632	Destabilizing	0.998	D	0.599	neutral	None	None	None	None	N
H/V	0.4509	ambiguous	0.3984	ambiguous	-0.937	Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
H/W	0.5739	likely_pathogenic	0.5633	ambiguous	0.731	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
H/Y	0.1003	likely_benign	0.0826	benign	0.475	Stabilizing	0.4	N	0.447	neutral	N	0.405878206	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.