TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20786	62581;62582;62583	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
N2AB	19145	57658;57659;57660	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
N2A	18218	54877;54878;54879	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
N2B	11721	35386;35387;35388	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
Novex-1	11846	35761;35762;35763	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
Novex-2	11913	35962;35963;35964	chr2:178589369;178589368;178589367	chr2:179454096;179454095;179454094
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-122
• Domain position: 18
• Structural Position: 26
• Q(SASA): 0.4426
• 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	None	None	0.454	N	0.349	0.07	0.139678290688	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
T/N	None	None	0.801	N	0.33	0.16	0.318252033908	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
T/A	0.0749	likely_benign	0.0784	benign	-0.774	Destabilizing	0.454	N	0.349	neutral	N	0.482280354	None	None	N
T/C	0.3847	ambiguous	0.4014	ambiguous	-0.463	Destabilizing	0.998	D	0.371	neutral	None	None	None	None	N
T/D	0.3123	likely_benign	0.377	ambiguous	-0.024	Destabilizing	0.842	D	0.315	neutral	None	None	None	None	N
T/E	0.35	ambiguous	0.4063	ambiguous	-0.046	Destabilizing	0.842	D	0.303	neutral	None	None	None	None	N
T/F	0.3085	likely_benign	0.3144	benign	-0.95	Destabilizing	0.991	D	0.439	neutral	None	None	None	None	N
T/G	0.2142	likely_benign	0.2307	benign	-1.002	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	N
T/H	0.3244	likely_benign	0.3532	ambiguous	-1.277	Destabilizing	0.998	D	0.42	neutral	None	None	None	None	N
T/I	0.1946	likely_benign	0.2084	benign	-0.267	Destabilizing	0.966	D	0.377	neutral	N	0.4666208	None	None	N
T/K	0.3973	ambiguous	0.4355	ambiguous	-0.65	Destabilizing	0.842	D	0.31	neutral	None	None	None	None	N
T/L	0.1315	likely_benign	0.1342	benign	-0.267	Destabilizing	0.842	D	0.32	neutral	None	None	None	None	N
T/M	0.1128	likely_benign	0.1119	benign	0.041	Stabilizing	0.998	D	0.372	neutral	None	None	None	None	N
T/N	0.1032	likely_benign	0.1158	benign	-0.516	Destabilizing	0.801	D	0.33	neutral	N	0.489590329	None	None	N
T/P	0.1049	likely_benign	0.1222	benign	-0.405	Destabilizing	0.005	N	0.143	neutral	N	0.447839707	None	None	N
T/Q	0.3064	likely_benign	0.3349	benign	-0.72	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	N
T/R	0.36	ambiguous	0.3816	ambiguous	-0.391	Destabilizing	0.974	D	0.378	neutral	None	None	None	None	N
T/S	0.0927	likely_benign	0.0964	benign	-0.822	Destabilizing	0.062	N	0.101	neutral	N	0.441161664	None	None	N
T/V	0.1308	likely_benign	0.1384	benign	-0.405	Destabilizing	0.915	D	0.269	neutral	None	None	None	None	N
T/W	0.7351	likely_pathogenic	0.7344	pathogenic	-0.86	Destabilizing	0.998	D	0.565	neutral	None	None	None	None	N
T/Y	0.3496	ambiguous	0.3726	ambiguous	-0.63	Destabilizing	0.991	D	0.44	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.