TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15047	45364;45365;45366	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
N2AB	13406	40441;40442;40443	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
N2A	12479	37660;37661;37662	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
N2B	5982	18169;18170;18171	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
Novex-1	6107	18544;18545;18546	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
Novex-2	6174	18745;18746;18747	chr2:178621685;178621684;178621683	chr2:179486412;179486411;179486410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-102
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4283
• 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/P	rs764583221	-0.441	0.966	N	0.375	0.565	0.467923293426	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
T/P	rs764583221	-0.441	0.966	N	0.375	0.565	0.467923293426	gnomAD-4.0.0	1.59476E-06	None	None	None	None	N	None	0	2.29389E-05	None	0	0	None	0	0	0	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	0.0862	likely_benign	0.088	benign	-0.638	Destabilizing	0.454	N	0.348	neutral	N	0.50581697	None	None	N
T/C	0.5827	likely_pathogenic	0.6327	pathogenic	-0.414	Destabilizing	0.998	D	0.36	neutral	None	None	None	None	N
T/D	0.3574	ambiguous	0.3671	ambiguous	0.142	Stabilizing	0.728	D	0.336	neutral	None	None	None	None	N
T/E	0.3203	likely_benign	0.329	benign	0.13	Stabilizing	0.842	D	0.325	neutral	None	None	None	None	N
T/F	0.3243	likely_benign	0.3477	ambiguous	-0.801	Destabilizing	0.991	D	0.462	neutral	None	None	None	None	N
T/G	0.2869	likely_benign	0.3151	benign	-0.873	Destabilizing	0.525	D	0.401	neutral	None	None	None	None	N
T/H	0.3158	likely_benign	0.3273	benign	-1.119	Destabilizing	0.974	D	0.45	neutral	None	None	None	None	N
T/I	0.2035	likely_benign	0.2116	benign	-0.113	Destabilizing	0.966	D	0.377	neutral	D	0.595204997	None	None	N
T/K	0.237	likely_benign	0.2393	benign	-0.561	Destabilizing	0.842	D	0.319	neutral	None	None	None	None	N
T/L	0.1434	likely_benign	0.1513	benign	-0.113	Destabilizing	0.915	D	0.317	neutral	None	None	None	None	N
T/M	0.1107	likely_benign	0.1177	benign	0.034	Stabilizing	0.998	D	0.351	neutral	None	None	None	None	N
T/N	0.1085	likely_benign	0.1174	benign	-0.466	Destabilizing	0.005	N	0.127	neutral	N	0.506268532	None	None	N
T/P	0.1547	likely_benign	0.1506	benign	-0.255	Destabilizing	0.966	D	0.375	neutral	N	0.51280061	None	None	N
T/Q	0.2652	likely_benign	0.2761	benign	-0.597	Destabilizing	0.974	D	0.379	neutral	None	None	None	None	N
T/R	0.1881	likely_benign	0.1895	benign	-0.352	Destabilizing	0.949	D	0.357	neutral	None	None	None	None	N
T/S	0.1106	likely_benign	0.1187	benign	-0.755	Destabilizing	0.062	N	0.123	neutral	N	0.463188494	None	None	N
T/V	0.1665	likely_benign	0.1788	benign	-0.255	Destabilizing	0.915	D	0.297	neutral	None	None	None	None	N
T/W	0.7192	likely_pathogenic	0.7412	pathogenic	-0.763	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
T/Y	0.3369	likely_benign	0.3671	ambiguous	-0.51	Destabilizing	0.991	D	0.458	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.