TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7210	21853;21854;21855	chr2:178723472;178723471;178723470	chr2:179588199;179588198;179588197
N2AB	6893	20902;20903;20904	chr2:178723472;178723471;178723470	chr2:179588199;179588198;179588197
N2A	5966	18121;18122;18123	chr2:178723472;178723471;178723470	chr2:179588199;179588198;179588197
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-56
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.1726
• 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
V/A	rs2078787546	None	0.081	N	0.488	0.236	0.571137827458	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs2078787546	None	0.081	N	0.488	0.236	0.571137827458	gnomAD-4.0.0	6.57151E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
V/M	rs2078788121	None	0.427	D	0.652	0.229	0.499154427049	gnomAD-4.0.0	2.73776E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59849E-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
V/A	0.1442	likely_benign	0.1532	benign	-1.656	Destabilizing	0.081	N	0.488	neutral	N	0.489517898	None	None	N
V/C	0.6821	likely_pathogenic	0.6892	pathogenic	-1.236	Destabilizing	0.958	D	0.639	neutral	None	None	None	None	N
V/D	0.3143	likely_benign	0.3173	benign	-1.528	Destabilizing	0.124	N	0.671	neutral	None	None	None	None	N
V/E	0.1754	likely_benign	0.1764	benign	-1.397	Destabilizing	0.001	N	0.548	neutral	N	0.474203242	None	None	N
V/F	0.121	likely_benign	0.1203	benign	-1.041	Destabilizing	0.331	N	0.67	neutral	None	None	None	None	N
V/G	0.2493	likely_benign	0.2717	benign	-2.099	Highly Destabilizing	0.301	N	0.663	neutral	N	0.508636111	None	None	N
V/H	0.3486	ambiguous	0.3474	ambiguous	-1.714	Destabilizing	0.667	D	0.684	prob.neutral	None	None	None	None	N
V/I	0.0702	likely_benign	0.0693	benign	-0.475	Destabilizing	0.001	N	0.282	neutral	None	None	None	None	N
V/K	0.1882	likely_benign	0.187	benign	-1.105	Destabilizing	0.124	N	0.665	neutral	None	None	None	None	N
V/L	0.1169	likely_benign	0.1168	benign	-0.475	Destabilizing	None	N	0.273	neutral	N	0.476494185	None	None	N
V/M	0.0853	likely_benign	0.0869	benign	-0.56	Destabilizing	0.427	N	0.652	neutral	D	0.531963466	None	None	N
V/N	0.2329	likely_benign	0.2366	benign	-1.161	Destabilizing	0.667	D	0.7	prob.neutral	None	None	None	None	N
V/P	0.9264	likely_pathogenic	0.9375	pathogenic	-0.837	Destabilizing	0.859	D	0.671	neutral	None	None	None	None	N
V/Q	0.1888	likely_benign	0.1869	benign	-1.142	Destabilizing	0.011	N	0.54	neutral	None	None	None	None	N
V/R	0.1467	likely_benign	0.1478	benign	-0.886	Destabilizing	0.497	N	0.686	prob.neutral	None	None	None	None	N
V/S	0.1873	likely_benign	0.1956	benign	-1.839	Destabilizing	0.22	N	0.666	neutral	None	None	None	None	N
V/T	0.1449	likely_benign	0.1466	benign	-1.578	Destabilizing	0.22	N	0.601	neutral	None	None	None	None	N
V/W	0.6082	likely_pathogenic	0.6027	pathogenic	-1.382	Destabilizing	0.958	D	0.699	prob.neutral	None	None	None	None	N
V/Y	0.4075	ambiguous	0.3984	ambiguous	-1.007	Destabilizing	0.667	D	0.673	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.