TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10064	30415;30416;30417	chr2:178704180;178704179;178704178	chr2:179568907;179568906;179568905
N2AB	9747	29464;29465;29466	chr2:178704180;178704179;178704178	chr2:179568907;179568906;179568905
N2A	8820	26683;26684;26685	chr2:178704180;178704179;178704178	chr2:179568907;179568906;179568905
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-85
• Domain position: 76
• Structural Position: 161
• Q(SASA): 0.5537
• 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
D/Y	None	None	0.427	None	0.492	0.185	0.373357554552	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79881E-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
D/A	0.2032	likely_benign	0.3023	benign	0.019	Stabilizing	0.042	N	0.333	neutral	None	None	None	None	N
D/C	0.7496	likely_pathogenic	0.8608	pathogenic	-0.153	Destabilizing	0.958	D	0.453	neutral	None	None	None	None	N
D/E	0.1947	likely_benign	0.2733	benign	-0.224	Destabilizing	0.081	N	0.357	neutral	None	None	None	None	N
D/F	0.5825	likely_pathogenic	0.7197	pathogenic	-0.065	Destabilizing	0.667	D	0.484	neutral	None	None	None	None	N
D/G	0.1273	likely_benign	0.1744	benign	-0.103	Destabilizing	None	N	0.132	neutral	None	None	None	None	N
D/H	0.2583	likely_benign	0.3685	ambiguous	0.517	Stabilizing	0.001	N	0.162	neutral	None	None	None	None	N
D/I	0.4538	ambiguous	0.623	pathogenic	0.275	Stabilizing	0.667	D	0.489	neutral	None	None	None	None	N
D/K	0.3414	ambiguous	0.4583	ambiguous	0.366	Stabilizing	0.22	N	0.367	neutral	None	None	None	None	N
D/L	0.4775	ambiguous	0.6122	pathogenic	0.275	Stabilizing	0.22	N	0.507	neutral	None	None	None	None	N
D/M	0.6589	likely_pathogenic	0.7988	pathogenic	0.055	Stabilizing	0.958	D	0.459	neutral	None	None	None	None	N
D/N	0.0801	likely_benign	0.1049	benign	0.194	Stabilizing	None	N	0.103	neutral	None	None	None	None	N
D/P	0.7969	likely_pathogenic	0.8911	pathogenic	0.21	Stabilizing	0.667	D	0.449	neutral	None	None	None	None	N
D/Q	0.3616	ambiguous	0.4992	ambiguous	0.193	Stabilizing	0.22	N	0.359	neutral	None	None	None	None	N
D/R	0.4013	ambiguous	0.5486	ambiguous	0.627	Stabilizing	0.22	N	0.496	neutral	None	None	None	None	N
D/S	0.1394	likely_benign	0.2018	benign	0.063	Stabilizing	0.002	N	0.1	neutral	None	None	None	None	N
D/T	0.263	likely_benign	0.3711	ambiguous	0.16	Stabilizing	0.124	N	0.337	neutral	None	None	None	None	N
D/V	0.2995	likely_benign	0.4399	ambiguous	0.21	Stabilizing	0.175	N	0.519	neutral	None	None	None	None	N
D/W	0.881	likely_pathogenic	0.9253	pathogenic	-0.026	Destabilizing	0.958	D	0.486	neutral	None	None	None	None	N
D/Y	0.227	likely_benign	0.3065	benign	0.159	Stabilizing	0.427	N	0.492	neutral	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.