TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35375	106348;106349;106350	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
N2AB	33734	101425;101426;101427	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
N2A	32807	98644;98645;98646	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
N2B	26310	79153;79154;79155	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
Novex-1	26435	79528;79529;79530	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
Novex-2	26502	79729;79730;79731	chr2:178530492;178530491;178530490	chr2:179395219;179395218;179395217
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: Ig-165
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.6201
• 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	None	None	None	N	0.188	0.065	0.128392430309	gnomAD-4.0.0	1.59093E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85753E-06	0	0
M/T	None	None	None	N	0.195	0.091	0.203808441222	gnomAD-4.0.0	2.05244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99399E-07	2.31868E-05	0
M/V	None	None	None	N	0.147	0.101	0.0954503805726	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

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	0.1513	likely_benign	0.1473	benign	-0.309	Destabilizing	None	N	0.199	neutral	None	None	None	None	N
M/C	0.5274	ambiguous	0.5179	ambiguous	-0.413	Destabilizing	0.041	N	0.353	neutral	None	None	None	None	N
M/D	0.4961	ambiguous	0.454	ambiguous	0.589	Stabilizing	0.002	N	0.385	neutral	None	None	None	None	N
M/E	0.2033	likely_benign	0.1904	benign	0.549	Stabilizing	0.001	N	0.335	neutral	None	None	None	None	N
M/F	0.2223	likely_benign	0.2223	benign	0.078	Stabilizing	0.009	N	0.227	neutral	None	None	None	None	N
M/G	0.3508	ambiguous	0.3257	benign	-0.488	Destabilizing	0.001	N	0.312	neutral	None	None	None	None	N
M/H	0.2672	likely_benign	0.2537	benign	0.359	Stabilizing	0.041	N	0.423	neutral	None	None	None	None	N
M/I	0.1518	likely_benign	0.1591	benign	0.068	Stabilizing	None	N	0.188	neutral	N	0.424768925	None	None	N
M/K	0.0835	likely_benign	0.0824	benign	0.532	Stabilizing	None	N	0.197	neutral	N	0.443007969	None	None	N
M/L	0.1064	likely_benign	0.1063	benign	0.068	Stabilizing	None	N	0.181	neutral	N	0.418149597	None	None	N
M/N	0.2401	likely_benign	0.2265	benign	0.615	Stabilizing	0.002	N	0.367	neutral	None	None	None	None	N
M/P	0.6362	likely_pathogenic	0.5393	ambiguous	-0.029	Destabilizing	0.008	N	0.391	neutral	None	None	None	None	N
M/Q	0.1213	likely_benign	0.1189	benign	0.496	Stabilizing	0.002	N	0.195	neutral	None	None	None	None	N
M/R	0.0872	likely_benign	0.0853	benign	0.967	Stabilizing	None	N	0.201	neutral	N	0.460822939	None	None	N
M/S	0.155	likely_benign	0.145	benign	0.126	Stabilizing	None	N	0.197	neutral	None	None	None	None	N
M/T	0.0651	likely_benign	0.0658	benign	0.195	Stabilizing	None	N	0.195	neutral	N	0.367680704	None	None	N
M/V	0.0695	likely_benign	0.0706	benign	-0.029	Destabilizing	None	N	0.147	neutral	N	0.372627951	None	None	N
M/W	0.4523	ambiguous	0.4131	ambiguous	0.073	Stabilizing	0.316	N	0.302	neutral	None	None	None	None	N
M/Y	0.441	ambiguous	0.4033	ambiguous	0.242	Stabilizing	0.018	N	0.39	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.