TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9103	27532;27533;27534	chr2:178712718;178712717;178712716	chr2:179577445;179577444;179577443
N2AB	8786	26581;26582;26583	chr2:178712718;178712717;178712716	chr2:179577445;179577444;179577443
N2A	7859	23800;23801;23802	chr2:178712718;178712717;178712716	chr2:179577445;179577444;179577443
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-76
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.2934
• 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
T/A	rs1351836200	-0.684	0.704	N	0.495	0.241	0.289847578895	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	1.92678E-04	None	0	0	1.47E-05	0	0
T/A	rs1351836200	-0.684	0.704	N	0.495	0.241	0.289847578895	gnomAD-4.0.0	1.31401E-05	None	None	None	None	N	None	0	0	None	0	1.92678E-04	None	0	0	1.46994E-05	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
T/A	0.0984	likely_benign	0.1018	benign	-0.738	Destabilizing	0.704	D	0.495	neutral	N	0.494531101	None	None	N
T/C	0.6179	likely_pathogenic	0.636	pathogenic	-0.3	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
T/D	0.4095	ambiguous	0.4636	ambiguous	-0.495	Destabilizing	0.939	D	0.556	neutral	None	None	None	None	N
T/E	0.2915	likely_benign	0.3411	ambiguous	-0.52	Destabilizing	0.884	D	0.55	neutral	None	None	None	None	N
T/F	0.3011	likely_benign	0.3039	benign	-0.909	Destabilizing	0.991	D	0.651	neutral	None	None	None	None	N
T/G	0.3193	likely_benign	0.3143	benign	-0.973	Destabilizing	0.939	D	0.625	neutral	None	None	None	None	N
T/H	0.2542	likely_benign	0.2628	benign	-1.32	Destabilizing	0.202	N	0.515	neutral	None	None	None	None	N
T/I	0.2083	likely_benign	0.2334	benign	-0.206	Destabilizing	0.988	D	0.593	neutral	N	0.504774997	None	None	N
T/K	0.159	likely_benign	0.1806	benign	-0.811	Destabilizing	0.852	D	0.536	neutral	N	0.485323935	None	None	N
T/L	0.141	likely_benign	0.1445	benign	-0.206	Destabilizing	0.969	D	0.533	neutral	None	None	None	None	N
T/M	0.1095	likely_benign	0.1077	benign	0.224	Stabilizing	0.999	D	0.561	neutral	None	None	None	None	N
T/N	0.1448	likely_benign	0.1596	benign	-0.65	Destabilizing	0.939	D	0.541	neutral	None	None	None	None	N
T/P	0.1571	likely_benign	0.1646	benign	-0.352	Destabilizing	0.035	N	0.334	neutral	N	0.514089781	None	None	N
T/Q	0.2002	likely_benign	0.2081	benign	-0.865	Destabilizing	0.579	D	0.349	neutral	None	None	None	None	N
T/R	0.1347	likely_benign	0.1488	benign	-0.51	Destabilizing	0.976	D	0.58	neutral	N	0.489847066	None	None	N
T/S	0.1121	likely_benign	0.1095	benign	-0.845	Destabilizing	0.31	N	0.354	neutral	N	0.481417215	None	None	N
T/V	0.1651	likely_benign	0.1761	benign	-0.352	Destabilizing	0.969	D	0.538	neutral	None	None	None	None	N
T/W	0.6839	likely_pathogenic	0.6837	pathogenic	-0.874	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
T/Y	0.3656	ambiguous	0.3859	ambiguous	-0.651	Destabilizing	0.982	D	0.658	neutral	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.