TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15604	47035;47036;47037	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
N2AB	13963	42112;42113;42114	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
N2A	13036	39331;39332;39333	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
N2B	6539	19840;19841;19842	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
Novex-1	6664	20215;20216;20217	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
Novex-2	6731	20416;20417;20418	chr2:178618740;178618739;178618738	chr2:179483467;179483466;179483465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-108
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.61
• 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
E/K	rs749463044	0.552	0.024	N	0.264	0.144	0.18995819373	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs749463044	0.552	0.024	N	0.264	0.144	0.18995819373	gnomAD-4.0.0	1.36996E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32051E-05	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
E/A	0.1549	likely_benign	0.2207	benign	-0.273	Destabilizing	None	N	0.173	neutral	N	0.449539738	None	None	N
E/C	0.7283	likely_pathogenic	0.8345	pathogenic	0.056	Stabilizing	0.676	D	0.407	neutral	None	None	None	None	N
E/D	0.0691	likely_benign	0.088	benign	-0.264	Destabilizing	None	N	0.107	neutral	N	0.387082963	None	None	N
E/F	0.6733	likely_pathogenic	0.7774	pathogenic	-0.22	Destabilizing	0.356	N	0.434	neutral	None	None	None	None	N
E/G	0.0734	likely_benign	0.0924	benign	-0.464	Destabilizing	None	N	0.17	neutral	N	0.422594015	None	None	N
E/H	0.4431	ambiguous	0.5856	pathogenic	-0.039	Destabilizing	0.356	N	0.275	neutral	None	None	None	None	N
E/I	0.4447	ambiguous	0.6056	pathogenic	0.192	Stabilizing	0.214	N	0.466	neutral	None	None	None	None	N
E/K	0.1974	likely_benign	0.2668	benign	0.387	Stabilizing	0.024	N	0.264	neutral	N	0.447515716	None	None	N
E/L	0.3731	ambiguous	0.5364	ambiguous	0.192	Stabilizing	0.038	N	0.504	neutral	None	None	None	None	N
E/M	0.452	ambiguous	0.6015	pathogenic	0.273	Stabilizing	0.628	D	0.407	neutral	None	None	None	None	N
E/N	0.1347	likely_benign	0.1693	benign	0.137	Stabilizing	None	N	0.123	neutral	None	None	None	None	N
E/P	0.7167	likely_pathogenic	0.8084	pathogenic	0.057	Stabilizing	0.136	N	0.467	neutral	None	None	None	None	N
E/Q	0.1589	likely_benign	0.2104	benign	0.168	Stabilizing	0.055	N	0.28	neutral	N	0.449729255	None	None	N
E/R	0.283	likely_benign	0.3509	ambiguous	0.536	Stabilizing	0.072	N	0.246	neutral	None	None	None	None	N
E/S	0.1714	likely_benign	0.2346	benign	-0.032	Destabilizing	0.016	N	0.215	neutral	None	None	None	None	N
E/T	0.2684	likely_benign	0.3963	ambiguous	0.122	Stabilizing	0.031	N	0.391	neutral	None	None	None	None	N
E/V	0.2834	likely_benign	0.4206	ambiguous	0.057	Stabilizing	0.029	N	0.488	neutral	N	0.451400123	None	None	N
E/W	0.7961	likely_pathogenic	0.8803	pathogenic	-0.107	Destabilizing	0.864	D	0.427	neutral	None	None	None	None	N
E/Y	0.4831	ambiguous	0.6097	pathogenic	0.017	Stabilizing	0.628	D	0.423	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.