TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5535	16828;16829;16830	chr2:178732458;178732457;178732456	chr2:179597185;179597184;179597183
N2AB	5218	15877;15878;15879	chr2:178732458;178732457;178732456	chr2:179597185;179597184;179597183
N2A	4291	13096;13097;13098	chr2:178732458;178732457;178732456	chr2:179597185;179597184;179597183
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-38
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.143
• 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
A/T	rs1442669083	-0.992	0.645	N	0.592	0.482	0.266385636622	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
A/T	rs1442669083	-0.992	0.645	N	0.592	0.482	0.266385636622	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1442669083	-0.992	0.645	N	0.592	0.482	0.266385636622	gnomAD-4.0.0	3.10908E-06	None	None	None	None	N	None	0	0	None	0	8.93535E-05	None	0	0	8.49946E-07	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
A/C	0.6076	likely_pathogenic	0.6252	pathogenic	-1.428	Destabilizing	0.995	D	0.66	neutral	None	None	None	None	N
A/D	0.7407	likely_pathogenic	0.7359	pathogenic	-1.508	Destabilizing	0.981	D	0.742	deleterious	None	None	None	None	N
A/E	0.7127	likely_pathogenic	0.6878	pathogenic	-1.545	Destabilizing	0.928	D	0.709	prob.delet.	D	0.529265716	None	None	N
A/F	0.755	likely_pathogenic	0.7125	pathogenic	-1.359	Destabilizing	0.809	D	0.717	prob.delet.	None	None	None	None	N
A/G	0.2154	likely_benign	0.226	benign	-1.274	Destabilizing	0.787	D	0.576	neutral	N	0.521250614	None	None	N
A/H	0.892	likely_pathogenic	0.8781	pathogenic	-1.356	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
A/I	0.5716	likely_pathogenic	0.5537	ambiguous	-0.553	Destabilizing	0.547	D	0.633	neutral	None	None	None	None	N
A/K	0.9184	likely_pathogenic	0.9108	pathogenic	-1.217	Destabilizing	0.945	D	0.708	prob.delet.	None	None	None	None	N
A/L	0.532	ambiguous	0.4933	ambiguous	-0.553	Destabilizing	0.007	N	0.455	neutral	None	None	None	None	N
A/M	0.5017	ambiguous	0.4809	ambiguous	-0.521	Destabilizing	0.894	D	0.723	prob.delet.	None	None	None	None	N
A/N	0.7116	likely_pathogenic	0.7057	pathogenic	-1.064	Destabilizing	0.981	D	0.736	prob.delet.	None	None	None	None	N
A/P	0.9673	likely_pathogenic	0.9669	pathogenic	-0.677	Destabilizing	0.975	D	0.723	prob.delet.	D	0.529519205	None	None	N
A/Q	0.7624	likely_pathogenic	0.7379	pathogenic	-1.276	Destabilizing	0.981	D	0.716	prob.delet.	None	None	None	None	N
A/R	0.8497	likely_pathogenic	0.832	pathogenic	-0.848	Destabilizing	0.945	D	0.716	prob.delet.	None	None	None	None	N
A/S	0.1254	likely_benign	0.132	benign	-1.441	Destabilizing	0.787	D	0.572	neutral	N	0.488498076	None	None	N
A/T	0.1142	likely_benign	0.1184	benign	-1.38	Destabilizing	0.645	D	0.592	neutral	N	0.478729201	None	None	N
A/V	0.253	likely_benign	0.2471	benign	-0.677	Destabilizing	0.024	N	0.405	neutral	N	0.5057583	None	None	N
A/W	0.9509	likely_pathogenic	0.9418	pathogenic	-1.615	Destabilizing	0.995	D	0.75	deleterious	None	None	None	None	N
A/Y	0.8823	likely_pathogenic	0.8583	pathogenic	-1.218	Destabilizing	0.945	D	0.735	prob.delet.	None	None	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.