TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6302	19129;19130;19131	chr2:178729134;178729133;178729132	chr2:179593861;179593860;179593859
N2AB	5985	18178;18179;18180	chr2:178729134;178729133;178729132	chr2:179593861;179593860;179593859
N2A	5058	15397;15398;15399	chr2:178729134;178729133;178729132	chr2:179593861;179593860;179593859
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-47
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4567
• 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/I	None	None	0.473	D	0.287	0.124	0.404034981753	gnomAD-4.0.0	6.90047E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04143E-07	0	0
T/N	rs766831279	-0.027	0.642	N	0.18	0.13	0.380052290102	gnomAD-2.1.1	1.13E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.46E-05	0
T/N	rs766831279	-0.027	0.642	N	0.18	0.13	0.380052290102	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
T/N	rs766831279	-0.027	0.642	N	0.18	0.13	0.380052290102	gnomAD-4.0.0	3.12243E-06	None	None	None	None	N	None	0	3.42654E-05	None	0	0	None	0	0	2.5553E-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
T/A	0.0772	likely_benign	0.0703	benign	-0.464	Destabilizing	0.425	N	0.257	neutral	D	0.527632295	None	None	N
T/C	0.4946	ambiguous	0.4915	ambiguous	-0.343	Destabilizing	0.995	D	0.335	neutral	None	None	None	None	N
T/D	0.4252	ambiguous	0.3982	ambiguous	0.241	Stabilizing	0.007	N	0.217	neutral	None	None	None	None	N
T/E	0.3042	likely_benign	0.2916	benign	0.189	Stabilizing	0.031	N	0.217	neutral	None	None	None	None	N
T/F	0.2387	likely_benign	0.244	benign	-0.819	Destabilizing	0.893	D	0.383	neutral	None	None	None	None	N
T/G	0.297	likely_benign	0.2624	benign	-0.637	Destabilizing	0.704	D	0.324	neutral	None	None	None	None	N
T/H	0.2633	likely_benign	0.2553	benign	-0.911	Destabilizing	0.017	N	0.237	neutral	None	None	None	None	N
T/I	0.1517	likely_benign	0.149	benign	-0.123	Destabilizing	0.473	N	0.287	neutral	D	0.53413698	None	None	N
T/K	0.1863	likely_benign	0.1849	benign	-0.435	Destabilizing	0.704	D	0.298	neutral	None	None	None	None	N
T/L	0.0998	likely_benign	0.1014	benign	-0.123	Destabilizing	0.144	N	0.319	neutral	None	None	None	None	N
T/M	0.0885	likely_benign	0.0905	benign	0.01	Stabilizing	0.176	N	0.257	neutral	None	None	None	None	N
T/N	0.1425	likely_benign	0.1328	benign	-0.27	Destabilizing	0.642	D	0.18	neutral	N	0.485327616	None	None	N
T/P	0.2188	likely_benign	0.1924	benign	-0.206	Destabilizing	0.917	D	0.408	neutral	N	0.508231264	None	None	N
T/Q	0.2163	likely_benign	0.208	benign	-0.463	Destabilizing	0.704	D	0.383	neutral	None	None	None	None	N
T/R	0.1402	likely_benign	0.1465	benign	-0.187	Destabilizing	0.704	D	0.405	neutral	None	None	None	None	N
T/S	0.1165	likely_benign	0.1063	benign	-0.52	Destabilizing	0.425	N	0.213	neutral	N	0.431548543	None	None	N
T/V	0.1086	likely_benign	0.1079	benign	-0.206	Destabilizing	0.013	N	0.082	neutral	None	None	None	None	N
T/W	0.5952	likely_pathogenic	0.5933	pathogenic	-0.798	Destabilizing	0.995	D	0.345	neutral	None	None	None	None	N
T/Y	0.2846	likely_benign	0.286	benign	-0.527	Destabilizing	0.893	D	0.394	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.