TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5929	18010;18011;18012	chr2:178730748;178730747;178730746	chr2:179595475;179595474;179595473
N2AB	5612	17059;17060;17061	chr2:178730748;178730747;178730746	chr2:179595475;179595474;179595473
N2A	4685	14278;14279;14280	chr2:178730748;178730747;178730746	chr2:179595475;179595474;179595473
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-43
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4907
• 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/N	None	None	0.989	N	0.464	0.28	0.32306181527	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	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
D/A	0.37	ambiguous	0.3756	ambiguous	-0.358	Destabilizing	0.978	D	0.513	neutral	N	0.489785983	None	None	N
D/C	0.9037	likely_pathogenic	0.9059	pathogenic	-0.011	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/E	0.2576	likely_benign	0.2851	benign	-0.442	Destabilizing	0.198	N	0.162	neutral	N	0.441992036	None	None	N
D/F	0.8249	likely_pathogenic	0.8351	pathogenic	-0.259	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/G	0.3865	ambiguous	0.4012	ambiguous	-0.594	Destabilizing	0.989	D	0.509	neutral	D	0.532654112	None	None	N
D/H	0.5458	ambiguous	0.5623	ambiguous	-0.284	Destabilizing	1.0	D	0.649	neutral	N	0.500504409	None	None	N
D/I	0.5942	likely_pathogenic	0.6305	pathogenic	0.223	Stabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
D/K	0.7431	likely_pathogenic	0.775	pathogenic	0.113	Stabilizing	0.983	D	0.514	neutral	None	None	None	None	N
D/L	0.6798	likely_pathogenic	0.713	pathogenic	0.223	Stabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
D/M	0.8492	likely_pathogenic	0.8653	pathogenic	0.45	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
D/N	0.1782	likely_benign	0.2038	benign	-0.189	Destabilizing	0.989	D	0.464	neutral	N	0.451595741	None	None	N
D/P	0.8886	likely_pathogenic	0.9085	pathogenic	0.053	Stabilizing	0.999	D	0.661	neutral	None	None	None	None	N
D/Q	0.6142	likely_pathogenic	0.6387	pathogenic	-0.149	Destabilizing	0.995	D	0.549	neutral	None	None	None	None	N
D/R	0.768	likely_pathogenic	0.7822	pathogenic	0.266	Stabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
D/S	0.2649	likely_benign	0.2804	benign	-0.325	Destabilizing	0.983	D	0.383	neutral	None	None	None	None	N
D/T	0.3937	ambiguous	0.4287	ambiguous	-0.145	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
D/V	0.3556	ambiguous	0.3805	ambiguous	0.053	Stabilizing	0.997	D	0.718	prob.delet.	N	0.483454656	None	None	N
D/W	0.9627	likely_pathogenic	0.9656	pathogenic	-0.121	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/Y	0.4516	ambiguous	0.4765	ambiguous	-0.026	Destabilizing	1.0	D	0.727	prob.delet.	N	0.482092006	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.