TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14178	42757;42758;42759	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
N2AB	12537	37834;37835;37836	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
N2A	11610	35053;35054;35055	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
N2B	5113	15562;15563;15564	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
Novex-1	5238	15937;15938;15939	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
Novex-2	5305	16138;16139;16140	chr2:178633967;178633966;178633965	chr2:179498694;179498693;179498692
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-92
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.9179
• 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	0.997	N	0.45	0.33	0.168933306366	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.2635	likely_benign	0.2697	benign	-0.159	Destabilizing	0.978	D	0.417	neutral	N	0.487791	None	None	N
D/C	0.761	likely_pathogenic	0.7869	pathogenic	-0.126	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
D/E	0.1926	likely_benign	0.1823	benign	-0.216	Destabilizing	0.37	N	0.304	neutral	N	0.436789163	None	None	N
D/F	0.7625	likely_pathogenic	0.7581	pathogenic	0.009	Stabilizing	1.0	D	0.535	neutral	None	None	None	None	N
D/G	0.1422	likely_benign	0.1523	benign	-0.353	Destabilizing	0.121	N	0.321	neutral	N	0.409159186	None	None	N
D/H	0.3741	ambiguous	0.4134	ambiguous	0.38	Stabilizing	1.0	D	0.447	neutral	D	0.531247628	None	None	N
D/I	0.6075	likely_pathogenic	0.607	pathogenic	0.305	Stabilizing	0.999	D	0.562	neutral	None	None	None	None	N
D/K	0.3992	ambiguous	0.4588	ambiguous	0.313	Stabilizing	0.995	D	0.45	neutral	None	None	None	None	N
D/L	0.6032	likely_pathogenic	0.6151	pathogenic	0.305	Stabilizing	0.998	D	0.553	neutral	None	None	None	None	N
D/M	0.7563	likely_pathogenic	0.7645	pathogenic	0.231	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	N
D/N	0.1024	likely_benign	0.0975	benign	-0.035	Destabilizing	0.997	D	0.45	neutral	N	0.450407411	None	None	N
D/P	0.8615	likely_pathogenic	0.9009	pathogenic	0.172	Stabilizing	0.999	D	0.464	neutral	None	None	None	None	N
D/Q	0.4065	ambiguous	0.4474	ambiguous	0.022	Stabilizing	0.995	D	0.466	neutral	None	None	None	None	N
D/R	0.4725	ambiguous	0.5422	ambiguous	0.592	Stabilizing	0.995	D	0.445	neutral	None	None	None	None	N
D/S	0.1534	likely_benign	0.1516	benign	-0.154	Destabilizing	0.983	D	0.412	neutral	None	None	None	None	N
D/T	0.3467	ambiguous	0.3462	ambiguous	0.008	Stabilizing	0.998	D	0.465	neutral	None	None	None	None	N
D/V	0.4288	ambiguous	0.4227	ambiguous	0.172	Stabilizing	0.997	D	0.561	neutral	D	0.532893133	None	None	N
D/W	0.9366	likely_pathogenic	0.9487	pathogenic	0.147	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	N
D/Y	0.3768	ambiguous	0.397	ambiguous	0.255	Stabilizing	1.0	D	0.54	neutral	D	0.531437662	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.