TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29967	90124;90125;90126	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
N2AB	28326	85201;85202;85203	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
N2A	27399	82420;82421;82422	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
N2B	20902	62929;62930;62931	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
Novex-1	21027	63304;63305;63306	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
Novex-2	21094	63505;63506;63507	chr2:178553001;178553000;178552999	chr2:179417728;179417727;179417726
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-106
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.1163
• 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
N/S	rs1419503534	None	0.998	N	0.445	0.336	0.266385636622	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs1419503534	None	0.998	N	0.445	0.336	0.266385636622	gnomAD-4.0.0	1.86135E-06	None	None	None	None	N	None	2.66937E-05	0	None	0	0	None	0	0	0	0	1.60159E-05

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
N/A	0.5706	likely_pathogenic	0.5001	ambiguous	-1.109	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
N/C	0.4452	ambiguous	0.3703	ambiguous	-0.243	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
N/D	0.4137	ambiguous	0.3635	ambiguous	-0.838	Destabilizing	0.998	D	0.484	neutral	N	0.486181357	None	None	N
N/E	0.8462	likely_pathogenic	0.8135	pathogenic	-0.72	Destabilizing	0.997	D	0.517	neutral	None	None	None	None	N
N/F	0.8509	likely_pathogenic	0.8193	pathogenic	-0.789	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
N/G	0.3381	likely_benign	0.3012	benign	-1.459	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	N
N/H	0.1173	likely_benign	0.0991	benign	-1.046	Destabilizing	0.64	D	0.393	neutral	N	0.479904558	None	None	N
N/I	0.9003	likely_pathogenic	0.8608	pathogenic	-0.206	Destabilizing	1.0	D	0.899	deleterious	N	0.494601601	None	None	N
N/K	0.7068	likely_pathogenic	0.6297	pathogenic	-0.317	Destabilizing	0.998	D	0.537	neutral	N	0.478063828	None	None	N
N/L	0.7859	likely_pathogenic	0.7354	pathogenic	-0.206	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
N/M	0.8494	likely_pathogenic	0.8117	pathogenic	0.278	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
N/P	0.9873	likely_pathogenic	0.9846	pathogenic	-0.478	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
N/Q	0.6184	likely_pathogenic	0.5517	ambiguous	-1.003	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
N/R	0.6034	likely_pathogenic	0.5324	ambiguous	-0.286	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
N/S	0.1034	likely_benign	0.0928	benign	-1.068	Destabilizing	0.998	D	0.445	neutral	N	0.504914859	None	None	N
N/T	0.4794	ambiguous	0.4129	ambiguous	-0.755	Destabilizing	0.999	D	0.553	neutral	N	0.487573709	None	None	N
N/V	0.8867	likely_pathogenic	0.8464	pathogenic	-0.478	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
N/W	0.9297	likely_pathogenic	0.9125	pathogenic	-0.479	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
N/Y	0.3873	ambiguous	0.3384	benign	-0.285	Destabilizing	0.999	D	0.856	deleterious	N	0.468330591	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.