TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9557	28894;28895;28896	chr2:178709650;178709649;178709648	chr2:179574377;179574376;179574375
N2AB	9240	27943;27944;27945	chr2:178709650;178709649;178709648	chr2:179574377;179574376;179574375
N2A	8313	25162;25163;25164	chr2:178709650;178709649;178709648	chr2:179574377;179574376;179574375
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-81
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.2623
• 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
G/D	None	None	None	None	0.147	0.145	0.197625483188	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/R	rs1560553033	None	0.055	None	0.437	0.121	0.342865806769	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
G/R	rs1560553033	None	0.055	None	0.437	0.121	0.342865806769	gnomAD-4.0.0	3.42091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5978E-06	0	1.65645E-05

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
G/A	0.0856	likely_benign	0.0787	benign	-0.85	Destabilizing	0.005	N	0.272	neutral	None	None	None	None	N
G/C	0.1503	likely_benign	0.1469	benign	-1.074	Destabilizing	0.612	D	0.465	neutral	None	None	None	None	N
G/D	0.1411	likely_benign	0.119	benign	-1.488	Destabilizing	None	N	0.147	neutral	None	None	None	None	N
G/E	0.1355	likely_benign	0.1221	benign	-1.601	Destabilizing	None	N	0.117	neutral	None	None	None	None	N
G/F	0.4043	ambiguous	0.3484	ambiguous	-1.43	Destabilizing	0.356	N	0.478	neutral	None	None	None	None	N
G/H	0.2323	likely_benign	0.2055	benign	-1.249	Destabilizing	0.001	N	0.29	neutral	None	None	None	None	N
G/I	0.2011	likely_benign	0.18	benign	-0.689	Destabilizing	0.214	N	0.467	neutral	None	None	None	None	N
G/K	0.2235	likely_benign	0.197	benign	-1.318	Destabilizing	0.016	N	0.428	neutral	None	None	None	None	N
G/L	0.2537	likely_benign	0.2286	benign	-0.689	Destabilizing	0.072	N	0.454	neutral	None	None	None	None	N
G/M	0.3173	likely_benign	0.2845	benign	-0.463	Destabilizing	0.628	D	0.473	neutral	None	None	None	None	N
G/N	0.1515	likely_benign	0.1394	benign	-0.998	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
G/P	0.8721	likely_pathogenic	0.8473	pathogenic	-0.705	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	N
G/Q	0.1864	likely_benign	0.1669	benign	-1.303	Destabilizing	0.001	N	0.145	neutral	None	None	None	None	N
G/R	0.1491	likely_benign	0.1282	benign	-0.824	Destabilizing	0.055	N	0.437	neutral	None	None	None	None	N
G/S	0.0638	likely_benign	0.0604	benign	-1.173	Destabilizing	None	N	0.107	neutral	None	None	None	None	N
G/T	0.097	likely_benign	0.093	benign	-1.223	Destabilizing	0.016	N	0.438	neutral	None	None	None	None	N
G/V	0.129	likely_benign	0.119	benign	-0.705	Destabilizing	0.055	N	0.448	neutral	None	None	None	None	N
G/W	0.3615	ambiguous	0.3323	benign	-1.651	Destabilizing	0.864	D	0.463	neutral	None	None	None	None	N
G/Y	0.3356	likely_benign	0.2841	benign	-1.297	Destabilizing	0.214	N	0.47	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.