TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6063	18412;18413;18414	chr2:178730213;178730212;178730211	chr2:179594940;179594939;179594938
N2AB	5746	17461;17462;17463	chr2:178730213;178730212;178730211	chr2:179594940;179594939;179594938
N2A	4819	14680;14681;14682	chr2:178730213;178730212;178730211	chr2:179594940;179594939;179594938
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: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-44
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5446
• 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/G	None	None	0.992	N	0.659	0.535	0.366848117066	gnomAD-4.0.0	1.59195E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-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
D/A	0.3542	ambiguous	0.4093	ambiguous	-0.652	Destabilizing	0.999	D	0.674	neutral	N	0.519802245	None	None	N
D/C	0.8738	likely_pathogenic	0.8965	pathogenic	-0.234	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/E	0.2709	likely_benign	0.3067	benign	-0.416	Destabilizing	0.992	D	0.404	neutral	N	0.426582653	None	None	N
D/F	0.8193	likely_pathogenic	0.8542	pathogenic	-0.09	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
D/G	0.2096	likely_benign	0.2604	benign	-0.965	Destabilizing	0.992	D	0.659	neutral	N	0.504507506	None	None	N
D/H	0.5877	likely_pathogenic	0.6357	pathogenic	-0.084	Destabilizing	1.0	D	0.709	prob.delet.	N	0.509294448	None	None	N
D/I	0.7247	likely_pathogenic	0.759	pathogenic	0.171	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
D/K	0.6442	likely_pathogenic	0.7003	pathogenic	-0.075	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
D/L	0.6613	likely_pathogenic	0.6924	pathogenic	0.171	Stabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
D/M	0.8034	likely_pathogenic	0.8281	pathogenic	0.494	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/N	0.1435	likely_benign	0.161	benign	-0.683	Destabilizing	0.79	D	0.295	neutral	N	0.494770515	None	None	N
D/P	0.9336	likely_pathogenic	0.9518	pathogenic	-0.08	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/Q	0.614	likely_pathogenic	0.6573	pathogenic	-0.545	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
D/R	0.7023	likely_pathogenic	0.7418	pathogenic	0.213	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
D/S	0.2218	likely_benign	0.2594	benign	-0.855	Destabilizing	0.994	D	0.602	neutral	None	None	None	None	N
D/T	0.3664	ambiguous	0.4128	ambiguous	-0.585	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
D/V	0.4834	ambiguous	0.5255	ambiguous	-0.08	Destabilizing	1.0	D	0.736	prob.delet.	N	0.489922745	None	None	N
D/W	0.9533	likely_pathogenic	0.9604	pathogenic	0.212	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
D/Y	0.4709	ambiguous	0.5149	ambiguous	0.186	Stabilizing	1.0	D	0.727	prob.delet.	N	0.498191632	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.