TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9912	29959;29960;29961	chr2:178704738;178704737;178704736	chr2:179569465;179569464;179569463
N2AB	9595	29008;29009;29010	chr2:178704738;178704737;178704736	chr2:179569465;179569464;179569463
N2A	8668	26227;26228;26229	chr2:178704738;178704737;178704736	chr2:179569465;179569464;179569463
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-84
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5189
• 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/W	None	None	0.997	None	0.476	0.311	0.754980121303	gnomAD-4.0.0	1.59922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-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	0.4974	ambiguous	0.5664	pathogenic	-1.011	Destabilizing	0.525	D	0.387	neutral	None	None	None	None	N
L/C	0.7912	likely_pathogenic	0.8449	pathogenic	-0.761	Destabilizing	0.998	D	0.391	neutral	None	None	None	None	N
L/D	0.8971	likely_pathogenic	0.9175	pathogenic	-0.447	Destabilizing	0.728	D	0.486	neutral	None	None	None	None	N
L/E	0.5623	ambiguous	0.6047	pathogenic	-0.5	Destabilizing	0.016	N	0.399	neutral	None	None	None	None	N
L/F	0.2898	likely_benign	0.3273	benign	-0.735	Destabilizing	0.012	N	0.158	neutral	None	None	None	None	N
L/G	0.8143	likely_pathogenic	0.8539	pathogenic	-1.241	Destabilizing	0.842	D	0.474	neutral	None	None	None	None	N
L/H	0.5449	ambiguous	0.6157	pathogenic	-0.368	Destabilizing	0.993	D	0.468	neutral	None	None	None	None	N
L/I	0.1766	likely_benign	0.1905	benign	-0.501	Destabilizing	0.016	N	0.227	neutral	None	None	None	None	N
L/K	0.4637	ambiguous	0.5143	ambiguous	-0.7	Destabilizing	0.728	D	0.489	neutral	None	None	None	None	N
L/M	0.1867	likely_benign	0.2092	benign	-0.481	Destabilizing	0.966	D	0.336	neutral	None	None	None	None	N
L/N	0.7332	likely_pathogenic	0.7738	pathogenic	-0.556	Destabilizing	0.949	D	0.478	neutral	None	None	None	None	N
L/P	0.572	likely_pathogenic	0.6474	pathogenic	-0.637	Destabilizing	0.974	D	0.493	neutral	None	None	None	None	N
L/Q	0.3077	likely_benign	0.3516	ambiguous	-0.759	Destabilizing	0.904	D	0.486	neutral	None	None	None	None	N
L/R	0.386	ambiguous	0.4322	ambiguous	-0.074	Destabilizing	0.949	D	0.485	neutral	None	None	None	None	N
L/S	0.5815	likely_pathogenic	0.6487	pathogenic	-1.071	Destabilizing	0.136	N	0.354	neutral	None	None	None	None	N
L/T	0.4326	ambiguous	0.4742	ambiguous	-1.014	Destabilizing	0.067	N	0.275	neutral	None	None	None	None	N
L/V	0.1875	likely_benign	0.2111	benign	-0.637	Destabilizing	0.454	N	0.359	neutral	None	None	None	None	N
L/W	0.5354	ambiguous	0.5908	pathogenic	-0.757	Destabilizing	0.997	D	0.476	neutral	None	None	None	None	N
L/Y	0.6649	likely_pathogenic	0.7244	pathogenic	-0.539	Destabilizing	0.904	D	0.399	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.