TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22839	68740;68741;68742	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
N2AB	21198	63817;63818;63819	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
N2A	20271	61036;61037;61038	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
N2B	13774	41545;41546;41547	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
Novex-1	13899	41920;41921;41922	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
Novex-2	13966	42121;42122;42123	chr2:178578000;178577999;178577998	chr2:179442727;179442726;179442725
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: Fn3-53
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.5331
• 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	1.0	N	0.736	0.526	0.794652452828	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
L/V	None	None	0.997	N	0.569	0.183	0.467329424371	gnomAD-4.0.0	1.5935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86138E-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
L/A	0.4995	ambiguous	0.5782	pathogenic	-1.585	Destabilizing	0.998	D	0.73	deleterious	None	None	None	None	N
L/C	0.6443	likely_pathogenic	0.7075	pathogenic	-0.904	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/D	0.964	likely_pathogenic	0.9756	pathogenic	-1.17	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
L/E	0.7117	likely_pathogenic	0.7732	pathogenic	-1.209	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/F	0.3305	likely_benign	0.369	ambiguous	-1.301	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
L/G	0.8537	likely_pathogenic	0.8965	pathogenic	-1.861	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
L/H	0.5162	ambiguous	0.5878	pathogenic	-1.088	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
L/I	0.1537	likely_benign	0.1524	benign	-0.922	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
L/K	0.3964	ambiguous	0.454	ambiguous	-0.986	Destabilizing	0.999	D	0.724	deleterious	None	None	None	None	N
L/M	0.1533	likely_benign	0.1585	benign	-0.621	Destabilizing	0.999	D	0.713	prob.delet.	D	0.525205278	None	None	N
L/N	0.8011	likely_pathogenic	0.8481	pathogenic	-0.758	Destabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
L/P	0.9716	likely_pathogenic	0.9831	pathogenic	-1.111	Destabilizing	1.0	D	0.736	deleterious	N	0.474027096	None	None	N
L/Q	0.2781	likely_benign	0.3327	benign	-1.024	Destabilizing	1.0	D	0.718	prob.delet.	N	0.48618553	None	None	N
L/R	0.2553	likely_benign	0.3023	benign	-0.328	Destabilizing	0.999	D	0.742	deleterious	N	0.452438316	None	None	N
L/S	0.6515	likely_pathogenic	0.7219	pathogenic	-1.316	Destabilizing	0.999	D	0.736	deleterious	None	None	None	None	N
L/T	0.4535	ambiguous	0.5025	ambiguous	-1.248	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/V	0.1379	likely_benign	0.1397	benign	-1.111	Destabilizing	0.997	D	0.569	neutral	N	0.48664689	None	None	N
L/W	0.5444	ambiguous	0.6039	pathogenic	-1.329	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
L/Y	0.673	likely_pathogenic	0.7235	pathogenic	-1.106	Destabilizing	0.999	D	0.717	prob.delet.	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.