TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5187	15784;15785;15786	chr2:178733830;178733829;178733828	chr2:179598557;179598556;179598555
N2AB	4870	14833;14834;14835	chr2:178733830;178733829;178733828	chr2:179598557;179598556;179598555
N2A	3943	12052;12053;12054	chr2:178733830;178733829;178733828	chr2:179598557;179598556;179598555
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-35
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1778
• 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
L/P	None	None	0.999	D	0.897	0.854	0.90282609855	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9956E-07	0	0
L/Q	None	None	0.997	D	0.888	0.79	0.895693387583	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	2.51978E-05	None	0	0	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
L/A	0.8357	likely_pathogenic	0.8937	pathogenic	-2.503	Highly Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
L/C	0.8177	likely_pathogenic	0.8777	pathogenic	-1.767	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/D	0.9967	likely_pathogenic	0.9983	pathogenic	-3.123	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/E	0.9758	likely_pathogenic	0.9861	pathogenic	-2.822	Highly Destabilizing	0.998	D	0.89	deleterious	None	None	None	None	N
L/F	0.0972	likely_benign	0.1193	benign	-1.469	Destabilizing	0.995	D	0.787	deleterious	None	None	None	None	N
L/G	0.9642	likely_pathogenic	0.9795	pathogenic	-3.084	Highly Destabilizing	0.998	D	0.888	deleterious	None	None	None	None	N
L/H	0.8608	likely_pathogenic	0.915	pathogenic	-2.598	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/I	0.1269	likely_benign	0.1436	benign	-0.777	Destabilizing	0.966	D	0.608	neutral	None	None	None	None	N
L/K	0.9434	likely_pathogenic	0.9673	pathogenic	-2.016	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
L/M	0.1409	likely_benign	0.1605	benign	-0.836	Destabilizing	0.898	D	0.547	neutral	D	0.57361859	None	None	N
L/N	0.9781	likely_pathogenic	0.9881	pathogenic	-2.622	Highly Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
L/P	0.9882	likely_pathogenic	0.9917	pathogenic	-1.34	Destabilizing	0.999	D	0.897	deleterious	D	0.843746367	None	None	N
L/Q	0.8464	likely_pathogenic	0.9017	pathogenic	-2.332	Highly Destabilizing	0.997	D	0.888	deleterious	D	0.843746367	None	None	N
L/R	0.8901	likely_pathogenic	0.9315	pathogenic	-2.019	Highly Destabilizing	0.997	D	0.881	deleterious	D	0.843746367	None	None	N
L/S	0.9365	likely_pathogenic	0.9643	pathogenic	-3.235	Highly Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	N
L/T	0.8951	likely_pathogenic	0.937	pathogenic	-2.768	Highly Destabilizing	0.995	D	0.806	deleterious	None	None	None	None	N
L/V	0.17	likely_benign	0.2038	benign	-1.34	Destabilizing	0.955	D	0.636	neutral	D	0.704838234	None	None	N
L/W	0.5119	ambiguous	0.6072	pathogenic	-1.822	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/Y	0.6236	likely_pathogenic	0.7189	pathogenic	-1.549	Destabilizing	0.998	D	0.823	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.