TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24066	72421;72422;72423	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
N2AB	22425	67498;67499;67500	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
N2A	21498	64717;64718;64719	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
N2B	15001	45226;45227;45228	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
Novex-1	15126	45601;45602;45603	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
Novex-2	15193	45802;45803;45804	chr2:178573936;178573935;178573934	chr2:179438663;179438662;179438661
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-131
• Domain position: 38
• Structural Position: 51
• Q(SASA): 0.6578
• 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	rs1357579405	0.335	0.007	N	0.215	0.124	0.222439326576	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
D/N	rs1357579405	0.335	0.007	N	0.215	0.124	0.222439326576	gnomAD-4.0.0	2.73767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59853E-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	0.1552	likely_benign	0.2085	benign	-0.126	Destabilizing	0.309	N	0.393	neutral	N	0.469435638	None	None	N
D/C	0.4925	ambiguous	0.572	pathogenic	0.21	Stabilizing	0.996	D	0.462	neutral	None	None	None	None	N
D/E	0.1474	likely_benign	0.1749	benign	-0.141	Destabilizing	0.003	N	0.161	neutral	N	0.465027865	None	None	N
D/F	0.5245	ambiguous	0.6442	pathogenic	-0.205	Destabilizing	0.835	D	0.461	neutral	None	None	None	None	N
D/G	0.1038	likely_benign	0.1376	benign	-0.272	Destabilizing	0.007	N	0.192	neutral	N	0.491323912	None	None	N
D/H	0.3135	likely_benign	0.3881	ambiguous	0.036	Stabilizing	0.884	D	0.377	neutral	D	0.530674164	None	None	N
D/I	0.4659	ambiguous	0.5836	pathogenic	0.197	Stabilizing	0.91	D	0.468	neutral	None	None	None	None	N
D/K	0.4276	ambiguous	0.4957	ambiguous	0.597	Stabilizing	0.59	D	0.37	neutral	None	None	None	None	N
D/L	0.3826	ambiguous	0.4903	ambiguous	0.197	Stabilizing	0.742	D	0.459	neutral	None	None	None	None	N
D/M	0.5719	likely_pathogenic	0.6787	pathogenic	0.299	Stabilizing	0.996	D	0.443	neutral	None	None	None	None	N
D/N	0.0882	likely_benign	0.1087	benign	0.344	Stabilizing	0.007	N	0.215	neutral	N	0.472119289	None	None	N
D/P	0.8825	likely_pathogenic	0.9358	pathogenic	0.11	Stabilizing	0.953	D	0.365	neutral	None	None	None	None	N
D/Q	0.3227	likely_benign	0.3831	ambiguous	0.359	Stabilizing	0.59	D	0.331	neutral	None	None	None	None	N
D/R	0.4224	ambiguous	0.4948	ambiguous	0.655	Stabilizing	0.91	D	0.411	neutral	None	None	None	None	N
D/S	0.1343	likely_benign	0.1712	benign	0.26	Stabilizing	0.59	D	0.272	neutral	None	None	None	None	N
D/T	0.3303	likely_benign	0.4279	ambiguous	0.378	Stabilizing	0.742	D	0.379	neutral	None	None	None	None	N
D/V	0.2754	likely_benign	0.3805	ambiguous	0.11	Stabilizing	0.684	D	0.472	neutral	N	0.487477441	None	None	N
D/W	0.8131	likely_pathogenic	0.8654	pathogenic	-0.131	Destabilizing	0.987	D	0.463	neutral	None	None	None	None	N
D/Y	0.1903	likely_benign	0.2429	benign	0.026	Stabilizing	0.015	N	0.369	neutral	N	0.519406764	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.