TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22513	67762;67763;67764	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
N2AB	20872	62839;62840;62841	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
N2A	19945	60058;60059;60060	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
N2B	13448	40567;40568;40569	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
Novex-1	13573	40942;40943;40944	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
Novex-2	13640	41143;41144;41145	chr2:178579660;178579659;178579658	chr2:179444387;179444386;179444385
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: Fn3-51
• Domain position: 63
• Structural Position: 97
• Q(SASA): 0.1319
• 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	0.851	0.446	0.559006825661	gnomAD-4.0.0	6.84372E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99648E-07	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	0.9005	likely_pathogenic	0.8901	pathogenic	-2.077	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
L/C	0.8614	likely_pathogenic	0.8141	pathogenic	-1.835	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/D	0.9968	likely_pathogenic	0.9967	pathogenic	-1.78	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/E	0.9845	likely_pathogenic	0.9834	pathogenic	-1.746	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/F	0.553	ambiguous	0.5332	ambiguous	-1.764	Destabilizing	1.0	D	0.877	deleterious	D	0.634562672	None	None	N
L/G	0.9719	likely_pathogenic	0.9704	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/H	0.9617	likely_pathogenic	0.9617	pathogenic	-1.617	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/I	0.2678	likely_benign	0.2529	benign	-1.176	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
L/K	0.9638	likely_pathogenic	0.9594	pathogenic	-1.376	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/M	0.2849	likely_benign	0.2535	benign	-1.053	Destabilizing	1.0	D	0.851	deleterious	D	0.584879437	None	None	N
L/N	0.9779	likely_pathogenic	0.9749	pathogenic	-1.354	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/P	0.9845	likely_pathogenic	0.9839	pathogenic	-1.449	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/Q	0.9273	likely_pathogenic	0.9217	pathogenic	-1.554	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/R	0.9383	likely_pathogenic	0.938	pathogenic	-0.779	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/S	0.9764	likely_pathogenic	0.9743	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.65138925	None	None	N
L/T	0.9124	likely_pathogenic	0.8944	pathogenic	-1.9	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.2939	likely_benign	0.2706	benign	-1.449	Destabilizing	0.999	D	0.85	deleterious	D	0.584677633	None	None	N
L/W	0.9211	likely_pathogenic	0.9205	pathogenic	-1.811	Destabilizing	1.0	D	0.765	deleterious	D	0.65138925	None	None	N
L/Y	0.9373	likely_pathogenic	0.9374	pathogenic	-1.554	Destabilizing	1.0	D	0.823	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.