TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24873	74842;74843;74844	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
N2AB	23232	69919;69920;69921	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
N2A	22305	67138;67139;67140	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
N2B	15808	47647;47648;47649	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
Novex-1	15933	48022;48023;48024	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
Novex-2	16000	48223;48224;48225	chr2:178571515;178571514;178571513	chr2:179436242;179436241;179436240
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: Fn3-68
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.0945
• 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/M	None	None	1.0	D	0.837	0.658	0.667698751994	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.9886	likely_pathogenic	0.9892	pathogenic	-2.64	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
L/C	0.9814	likely_pathogenic	0.9829	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9997	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/E	0.9976	likely_pathogenic	0.998	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/F	0.9295	likely_pathogenic	0.9358	pathogenic	-1.874	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/G	0.9942	likely_pathogenic	0.9954	pathogenic	-3.124	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/H	0.9962	likely_pathogenic	0.9969	pathogenic	-2.358	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/I	0.7182	likely_pathogenic	0.7087	pathogenic	-1.277	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/K	0.9939	likely_pathogenic	0.9953	pathogenic	-1.978	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/M	0.7023	likely_pathogenic	0.7123	pathogenic	-1.281	Destabilizing	1.0	D	0.837	deleterious	D	0.606470749	None	None	N
L/N	0.9967	likely_pathogenic	0.9975	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/P	0.9955	likely_pathogenic	0.9963	pathogenic	-1.709	Destabilizing	1.0	D	0.84	deleterious	D	0.656961202	None	None	N
L/Q	0.9915	likely_pathogenic	0.993	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.672980563	None	None	N
L/R	0.99	likely_pathogenic	0.9919	pathogenic	-1.491	Destabilizing	1.0	D	0.833	deleterious	D	0.672980563	None	None	N
L/S	0.9981	likely_pathogenic	0.9983	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/T	0.9923	likely_pathogenic	0.993	pathogenic	-2.649	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.7959	likely_pathogenic	0.7892	pathogenic	-1.709	Destabilizing	0.999	D	0.833	deleterious	D	0.593732054	None	None	N
L/W	0.9914	likely_pathogenic	0.9933	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
L/Y	0.9924	likely_pathogenic	0.9936	pathogenic	-1.828	Destabilizing	1.0	D	0.815	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.