TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2602	8029;8030;8031	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
N2AB	2602	8029;8030;8031	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
N2A	2602	8029;8030;8031	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
N2B	2556	7891;7892;7893	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
Novex-1	2556	7891;7892;7893	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
Novex-2	2556	7891;7892;7893	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885
Novex-3	2602	8029;8030;8031	chr2:178773160;178773159;178773158	chr2:179637887;179637886;179637885

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-15
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.0988
• 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
Y/C	None	None	1.0	D	0.885	0.91	0.78620880623	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8826E-05	0	0	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
Y/A	0.9889	likely_pathogenic	0.9842	pathogenic	-0.934	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/C	0.8804	likely_pathogenic	0.8206	pathogenic	-0.649	Destabilizing	1.0	D	0.885	deleterious	D	0.748598045	None	None	N
Y/D	0.9962	likely_pathogenic	0.995	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.748598045	None	None	N
Y/E	0.9976	likely_pathogenic	0.9969	pathogenic	-1.829	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/F	0.2117	likely_benign	0.2028	benign	-0.117	Destabilizing	0.999	D	0.676	prob.neutral	D	0.646389788	None	None	N
Y/G	0.9847	likely_pathogenic	0.9787	pathogenic	-1.317	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/H	0.9769	likely_pathogenic	0.9667	pathogenic	-1.423	Destabilizing	1.0	D	0.775	deleterious	D	0.749208973	None	None	N
Y/I	0.7342	likely_pathogenic	0.698	pathogenic	0.305	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/K	0.9974	likely_pathogenic	0.9962	pathogenic	-1.07	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.7379	likely_pathogenic	0.7094	pathogenic	0.305	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
Y/M	0.9199	likely_pathogenic	0.9043	pathogenic	0.032	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.977	likely_pathogenic	0.97	pathogenic	-1.953	Destabilizing	1.0	D	0.886	deleterious	D	0.748598045	None	None	N
Y/P	0.9969	likely_pathogenic	0.9957	pathogenic	-0.117	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/Q	0.9976	likely_pathogenic	0.9965	pathogenic	-1.408	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/R	0.9933	likely_pathogenic	0.9904	pathogenic	-1.775	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/S	0.9897	likely_pathogenic	0.985	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.748598045	None	None	N
Y/T	0.9912	likely_pathogenic	0.9875	pathogenic	-1.705	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/V	0.7097	likely_pathogenic	0.6731	pathogenic	-0.117	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
Y/W	0.8729	likely_pathogenic	0.8461	pathogenic	0.195	Stabilizing	1.0	D	0.769	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.