TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14979	45160;45161;45162	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
N2AB	13338	40237;40238;40239	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
N2A	12411	37456;37457;37458	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
N2B	5914	17965;17966;17967	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
Novex-1	6039	18340;18341;18342	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
Novex-2	6106	18541;18542;18543	chr2:178621987;178621986;178621985	chr2:179486714;179486713;179486712
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-101
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.2406
• 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	None	None	0.101	N	0.319	0.134	0.242244723065	gnomAD-4.0.0	6.86271E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01372E-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	0.4002	ambiguous	0.4166	ambiguous	-0.789	Destabilizing	0.94	D	0.383	neutral	None	None	None	None	N
A/D	0.1978	likely_benign	0.1998	benign	-0.353	Destabilizing	0.213	N	0.473	neutral	N	0.504616756	None	None	N
A/E	0.149	likely_benign	0.154	benign	-0.461	Destabilizing	0.418	N	0.431	neutral	None	None	None	None	N
A/F	0.2161	likely_benign	0.2367	benign	-0.785	Destabilizing	0.716	D	0.527	neutral	None	None	None	None	N
A/G	0.1363	likely_benign	0.1407	benign	-0.545	Destabilizing	0.183	N	0.308	neutral	N	0.511074059	None	None	N
A/H	0.3299	likely_benign	0.3444	ambiguous	-0.454	Destabilizing	0.836	D	0.474	neutral	None	None	None	None	N
A/I	0.1264	likely_benign	0.1384	benign	-0.304	Destabilizing	0.002	N	0.221	neutral	None	None	None	None	N
A/K	0.2611	likely_benign	0.2739	benign	-0.767	Destabilizing	0.418	N	0.434	neutral	None	None	None	None	N
A/L	0.1151	likely_benign	0.1282	benign	-0.304	Destabilizing	0.022	N	0.319	neutral	None	None	None	None	N
A/M	0.1342	likely_benign	0.1459	benign	-0.451	Destabilizing	0.027	N	0.233	neutral	None	None	None	None	N
A/N	0.1467	likely_benign	0.1511	benign	-0.507	Destabilizing	0.01	N	0.283	neutral	None	None	None	None	N
A/P	0.6908	likely_pathogenic	0.6925	pathogenic	-0.309	Destabilizing	0.523	D	0.473	neutral	D	0.551166902	None	None	N
A/Q	0.1898	likely_benign	0.2005	benign	-0.712	Destabilizing	0.836	D	0.495	neutral	None	None	None	None	N
A/R	0.2259	likely_benign	0.2343	benign	-0.325	Destabilizing	0.593	D	0.473	neutral	None	None	None	None	N
A/S	0.0827	likely_benign	0.0836	benign	-0.782	Destabilizing	0.009	N	0.165	neutral	N	0.452298891	None	None	N
A/T	0.0645	likely_benign	0.0636	benign	-0.799	Destabilizing	0.101	N	0.319	neutral	N	0.484499134	None	None	N
A/V	0.0774	likely_benign	0.0798	benign	-0.309	Destabilizing	0.001	N	0.118	neutral	N	0.429417781	None	None	N
A/W	0.5995	likely_pathogenic	0.6277	pathogenic	-0.974	Destabilizing	0.983	D	0.503	neutral	None	None	None	None	N
A/Y	0.3628	ambiguous	0.3898	ambiguous	-0.618	Destabilizing	0.836	D	0.506	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.