TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23306	70141;70142;70143	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
N2AB	21665	65218;65219;65220	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
N2A	20738	62437;62438;62439	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
N2B	14241	42946;42947;42948	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
Novex-1	14366	43321;43322;43323	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
Novex-2	14433	43522;43523;43524	chr2:178576216;178576215;178576214	chr2:179440943;179440942;179440941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-57
• Domain position: 67
• Structural Position: 97
• Q(SASA): 0.1153
• 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	D	0.857	0.917	0.905779748082	gnomAD-4.0.0	1.59296E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-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	0.9669	likely_pathogenic	0.9696	pathogenic	-2.676	Highly Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
L/C	0.9333	likely_pathogenic	0.9435	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/D	0.999	likely_pathogenic	0.9992	pathogenic	-3.14	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/E	0.9939	likely_pathogenic	0.9952	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/F	0.8808	likely_pathogenic	0.8964	pathogenic	-1.681	Destabilizing	1.0	D	0.871	deleterious	D	0.629222885	None	None	N
L/G	0.9882	likely_pathogenic	0.99	pathogenic	-3.228	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/H	0.9876	likely_pathogenic	0.9909	pathogenic	-2.695	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.655568214	None	None	N
L/I	0.3609	ambiguous	0.3941	ambiguous	-1.075	Destabilizing	0.999	D	0.822	deleterious	D	0.616373467	None	None	N
L/K	0.9816	likely_pathogenic	0.9852	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/M	0.5092	ambiguous	0.5433	ambiguous	-1.023	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/N	0.992	likely_pathogenic	0.994	pathogenic	-2.427	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/P	0.9938	likely_pathogenic	0.9944	pathogenic	-1.59	Destabilizing	1.0	D	0.857	deleterious	D	0.655568214	None	None	N
L/Q	0.975	likely_pathogenic	0.981	pathogenic	-2.313	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/R	0.9646	likely_pathogenic	0.9712	pathogenic	-1.745	Destabilizing	1.0	D	0.857	deleterious	D	0.630030102	None	None	N
L/S	0.9931	likely_pathogenic	0.9948	pathogenic	-3.115	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/T	0.9603	likely_pathogenic	0.9674	pathogenic	-2.747	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.4682	ambiguous	0.5178	ambiguous	-1.59	Destabilizing	0.999	D	0.831	deleterious	D	0.580730833	None	None	N
L/W	0.986	likely_pathogenic	0.9888	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/Y	0.986	likely_pathogenic	0.9887	pathogenic	-1.82	Destabilizing	1.0	D	0.831	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.