TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15073	45442;45443;45444	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
N2AB	13432	40519;40520;40521	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
N2A	12505	37738;37739;37740	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
N2B	6008	18247;18248;18249	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
Novex-1	6133	18622;18623;18624	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
Novex-2	6200	18823;18824;18825	chr2:178621607;178621606;178621605	chr2:179486334;179486333;179486332
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-102
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.3227
• 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/A	rs1444196912	-0.466	0.139	N	0.223	0.161	0.26547132957	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
T/A	rs1444196912	-0.466	0.139	N	0.223	0.161	0.26547132957	gnomAD-4.0.0	4.79256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39944E-06	0	1.65837E-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
T/A	0.101	likely_benign	0.1014	benign	-0.434	Destabilizing	0.139	N	0.223	neutral	N	0.487637419	None	None	N
T/C	0.586	likely_pathogenic	0.6688	pathogenic	-0.41	Destabilizing	0.995	D	0.329	neutral	None	None	None	None	N
T/D	0.2868	likely_benign	0.2658	benign	0.428	Stabilizing	0.828	D	0.349	neutral	None	None	None	None	N
T/E	0.3042	likely_benign	0.2739	benign	0.396	Stabilizing	0.828	D	0.345	neutral	None	None	None	None	N
T/F	0.4202	ambiguous	0.384	ambiguous	-0.842	Destabilizing	0.944	D	0.447	neutral	None	None	None	None	N
T/G	0.1809	likely_benign	0.2103	benign	-0.604	Destabilizing	0.001	N	0.163	neutral	None	None	None	None	N
T/H	0.313	likely_benign	0.3056	benign	-0.77	Destabilizing	0.981	D	0.372	neutral	None	None	None	None	N
T/I	0.431	ambiguous	0.3724	ambiguous	-0.098	Destabilizing	0.27	N	0.333	neutral	N	0.513755328	None	None	N
T/K	0.222	likely_benign	0.2076	benign	-0.296	Destabilizing	0.784	D	0.347	neutral	N	0.489024484	None	None	N
T/L	0.2002	likely_benign	0.1969	benign	-0.098	Destabilizing	0.329	N	0.332	neutral	None	None	None	None	N
T/M	0.1369	likely_benign	0.128	benign	-0.167	Destabilizing	0.944	D	0.339	neutral	None	None	None	None	N
T/N	0.091	likely_benign	0.0948	benign	-0.256	Destabilizing	0.704	D	0.223	neutral	None	None	None	None	N
T/P	0.2659	likely_benign	0.2531	benign	-0.18	Destabilizing	0.917	D	0.419	neutral	N	0.509901372	None	None	N
T/Q	0.2605	likely_benign	0.2548	benign	-0.352	Destabilizing	0.981	D	0.403	neutral	None	None	None	None	N
T/R	0.1991	likely_benign	0.1786	benign	-0.09	Destabilizing	0.927	D	0.417	neutral	N	0.483203616	None	None	N
T/S	0.1003	likely_benign	0.1045	benign	-0.509	Destabilizing	0.425	N	0.315	neutral	N	0.384206862	None	None	N
T/V	0.3245	likely_benign	0.3085	benign	-0.18	Destabilizing	0.013	N	0.147	neutral	None	None	None	None	N
T/W	0.6944	likely_pathogenic	0.7011	pathogenic	-0.874	Destabilizing	0.995	D	0.37	neutral	None	None	None	None	N
T/Y	0.3796	ambiguous	0.392	ambiguous	-0.567	Destabilizing	0.981	D	0.418	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.