TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16062	48409;48410;48411	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
N2AB	14421	43486;43487;43488	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
N2A	13494	40705;40706;40707	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
N2B	6997	21214;21215;21216	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
Novex-1	7122	21589;21590;21591	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
Novex-2	7189	21790;21791;21792	chr2:178616607;178616606;178616605	chr2:179481334;179481333;179481332
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: Fn3-4
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.192
• 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/F	None	None	0.217	D	0.453	0.105	0.379366414296	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8856	likely_pathogenic	0.9193	pathogenic	-2.263	Highly Destabilizing	0.996	D	0.769	deleterious	None	None	None	None	N
L/C	0.7828	likely_pathogenic	0.856	pathogenic	-1.6	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/D	0.9959	likely_pathogenic	0.997	pathogenic	-2.57	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/E	0.9807	likely_pathogenic	0.987	pathogenic	-2.329	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/F	0.3006	likely_benign	0.3402	ambiguous	-1.254	Destabilizing	0.217	N	0.453	neutral	D	0.528851179	None	None	N
L/G	0.9659	likely_pathogenic	0.9757	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/H	0.956	likely_pathogenic	0.9711	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/I	0.1381	likely_benign	0.1463	benign	-0.635	Destabilizing	0.992	D	0.725	prob.delet.	None	None	None	None	N
L/K	0.963	likely_pathogenic	0.9774	pathogenic	-1.705	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/M	0.2047	likely_benign	0.2282	benign	-0.689	Destabilizing	0.999	D	0.79	deleterious	D	0.63432653	None	None	N
L/N	0.9757	likely_pathogenic	0.982	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/P	0.8202	likely_pathogenic	0.8736	pathogenic	-1.158	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/Q	0.9342	likely_pathogenic	0.957	pathogenic	-1.872	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/R	0.9396	likely_pathogenic	0.9608	pathogenic	-1.563	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
L/S	0.9776	likely_pathogenic	0.9844	pathogenic	-2.744	Highly Destabilizing	0.999	D	0.852	deleterious	D	0.68196584	None	None	N
L/T	0.888	likely_pathogenic	0.9187	pathogenic	-2.35	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/V	0.1896	likely_benign	0.2149	benign	-1.158	Destabilizing	0.989	D	0.725	prob.delet.	N	0.492123082	None	None	N
L/W	0.7896	likely_pathogenic	0.8344	pathogenic	-1.687	Destabilizing	1.0	D	0.859	deleterious	D	0.743489538	None	None	N
L/Y	0.8586	likely_pathogenic	0.8979	pathogenic	-1.349	Destabilizing	0.995	D	0.825	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.