TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2716	8371;8372;8373	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
N2AB	2716	8371;8372;8373	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
N2A	2716	8371;8372;8373	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
N2B	2670	8233;8234;8235	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
Novex-1	2670	8233;8234;8235	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
Novex-2	2670	8233;8234;8235	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371
Novex-3	2716	8371;8372;8373	chr2:178770646;178770645;178770644	chr2:179635373;179635372;179635371

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-17
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3273
• 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	rs752870590	-0.756	0.984	D	0.59	0.608	0.861400942078	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
L/P	rs752870590	-0.756	0.984	D	0.59	0.608	0.861400942078	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/P	rs752870590	-0.756	0.984	D	0.59	0.608	0.861400942078	gnomAD-4.0.0	5.12554E-06	None	None	None	None	N	None	0	6.77897E-05	None	0	0	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	0.3066	likely_benign	0.343	ambiguous	-0.637	Destabilizing	0.919	D	0.441	neutral	None	None	None	None	N
L/C	0.561	ambiguous	0.5986	pathogenic	-0.668	Destabilizing	0.999	D	0.471	neutral	None	None	None	None	N
L/D	0.8396	likely_pathogenic	0.8772	pathogenic	-0.091	Destabilizing	0.976	D	0.538	neutral	None	None	None	None	N
L/E	0.3306	likely_benign	0.3694	ambiguous	-0.138	Destabilizing	0.851	D	0.495	neutral	None	None	None	None	N
L/F	0.2465	likely_benign	0.2733	benign	-0.531	Destabilizing	0.995	D	0.419	neutral	D	0.604200867	None	None	N
L/G	0.7817	likely_pathogenic	0.8268	pathogenic	-0.822	Destabilizing	0.976	D	0.536	neutral	None	None	None	None	N
L/H	0.3108	likely_benign	0.3501	ambiguous	-0.093	Destabilizing	0.996	D	0.605	neutral	D	0.606224862	None	None	N
L/I	0.0725	likely_benign	0.0738	benign	-0.248	Destabilizing	0.946	D	0.417	neutral	N	0.510168819	None	None	N
L/K	0.2626	likely_benign	0.2821	benign	-0.367	Destabilizing	0.851	D	0.477	neutral	None	None	None	None	N
L/M	0.0914	likely_benign	0.0884	benign	-0.537	Destabilizing	0.996	D	0.458	neutral	None	None	None	None	N
L/N	0.5376	ambiguous	0.5842	pathogenic	-0.257	Destabilizing	0.976	D	0.57	neutral	None	None	None	None	N
L/P	0.9818	likely_pathogenic	0.9889	pathogenic	-0.347	Destabilizing	0.984	D	0.59	neutral	D	0.606224862	None	None	N
L/Q	0.1082	likely_benign	0.1162	benign	-0.377	Destabilizing	0.06	N	0.289	neutral	None	None	None	None	N
L/R	0.2241	likely_benign	0.247	benign	0.055	Stabilizing	0.938	D	0.509	neutral	D	0.605246877	None	None	N
L/S	0.388	ambiguous	0.4445	ambiguous	-0.706	Destabilizing	0.919	D	0.499	neutral	None	None	None	None	N
L/T	0.2275	likely_benign	0.2405	benign	-0.639	Destabilizing	0.919	D	0.437	neutral	None	None	None	None	N
L/V	0.0786	likely_benign	0.0805	benign	-0.347	Destabilizing	0.946	D	0.452	neutral	N	0.481981847	None	None	N
L/W	0.4765	ambiguous	0.553	ambiguous	-0.59	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
L/Y	0.5068	ambiguous	0.5589	ambiguous	-0.337	Destabilizing	0.996	D	0.451	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.