TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22223	66892;66893;66894	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
N2AB	20582	61969;61970;61971	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
N2A	19655	59188;59189;59190	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
N2B	13158	39697;39698;39699	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
Novex-1	13283	40072;40073;40074	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
Novex-2	13350	40273;40274;40275	chr2:178581601;178581600;178581599	chr2:179446328;179446327;179446326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-49
• Domain position: 68
• Structural Position: 98
• Q(SASA): 0.6548
• 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
M/I	rs1049450842	-0.087	None	N	0.113	0.114	0.16115917748	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.71E-05	None	0	0	None	0	None	0	0	0
M/I	rs1049450842	-0.087	None	N	0.113	0.114	0.16115917748	gnomAD-4.0.0	4.10796E-06	None	None	None	None	N	None	0	6.71501E-05	None	0	0	None	0	0	2.69967E-06	0	0
M/K	rs752794705	0.484	0.055	N	0.299	0.201	0.336892272479	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
M/K	rs752794705	0.484	0.055	N	0.299	0.201	0.336892272479	gnomAD-4.0.0	3.42324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49942E-06	0	0
M/L	None	None	None	N	0.099	0.07	0.246773566709	gnomAD-4.0.0	3.60102E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93757E-06	0	0
M/T	rs752794705	0.001	None	N	0.106	0.155	0.497214377195	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
M/T	rs752794705	0.001	None	N	0.106	0.155	0.497214377195	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/T	rs752794705	0.001	None	N	0.106	0.155	0.497214377195	gnomAD-4.0.0	6.20091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.48015E-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
M/A	0.2015	likely_benign	0.2075	benign	-0.756	Destabilizing	0.007	N	0.213	neutral	None	None	None	None	N
M/C	0.5518	ambiguous	0.5679	pathogenic	-0.741	Destabilizing	0.628	D	0.285	neutral	None	None	None	None	N
M/D	0.6219	likely_pathogenic	0.6131	pathogenic	0.486	Stabilizing	None	N	0.168	neutral	None	None	None	None	N
M/E	0.2747	likely_benign	0.2662	benign	0.5	Stabilizing	0.016	N	0.303	neutral	None	None	None	None	N
M/F	0.3073	likely_benign	0.3207	benign	-0.03	Destabilizing	0.072	N	0.191	neutral	None	None	None	None	N
M/G	0.4556	ambiguous	0.4618	ambiguous	-1.013	Destabilizing	0.031	N	0.355	neutral	None	None	None	None	N
M/H	0.3317	likely_benign	0.3507	ambiguous	-0.039	Destabilizing	0.628	D	0.304	neutral	None	None	None	None	N
M/I	0.182	likely_benign	0.1704	benign	-0.137	Destabilizing	None	N	0.113	neutral	N	0.335661499	None	None	N
M/K	0.1357	likely_benign	0.1289	benign	0.235	Stabilizing	0.055	N	0.299	neutral	N	0.327673947	None	None	N
M/L	0.0982	likely_benign	0.0968	benign	-0.137	Destabilizing	None	N	0.099	neutral	N	0.355092622	None	None	N
M/N	0.3385	likely_benign	0.3326	benign	0.23	Stabilizing	0.038	N	0.374	neutral	None	None	None	None	N
M/P	0.5393	ambiguous	0.5286	ambiguous	-0.314	Destabilizing	0.136	N	0.39	neutral	None	None	None	None	N
M/Q	0.1301	likely_benign	0.1329	benign	0.206	Stabilizing	0.136	N	0.251	neutral	None	None	None	None	N
M/R	0.1645	likely_benign	0.1588	benign	0.617	Stabilizing	0.055	N	0.365	neutral	N	0.339160378	None	None	N
M/S	0.2212	likely_benign	0.2324	benign	-0.346	Destabilizing	0.016	N	0.257	neutral	None	None	None	None	N
M/T	0.1203	likely_benign	0.1181	benign	-0.208	Destabilizing	None	N	0.106	neutral	N	0.34918537	None	None	N
M/V	0.0806	likely_benign	0.0763	benign	-0.314	Destabilizing	0.001	N	0.149	neutral	N	0.385780888	None	None	N
M/W	0.5947	likely_pathogenic	0.6019	pathogenic	-0.027	Destabilizing	0.864	D	0.281	neutral	None	None	None	None	N
M/Y	0.5252	ambiguous	0.5346	ambiguous	0.078	Stabilizing	0.356	N	0.348	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.