TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5525	16798;16799;16800	chr2:178732488;178732487;178732486	chr2:179597215;179597214;179597213
N2AB	5208	15847;15848;15849	chr2:178732488;178732487;178732486	chr2:179597215;179597214;179597213
N2A	4281	13066;13067;13068	chr2:178732488;178732487;178732486	chr2:179597215;179597214;179597213
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-38
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2608
• 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
S/I	None	None	0.667	N	0.699	0.349	0.645206814577	gnomAD-4.0.0	1.36918E-06	None	None	None	None	N	None	5.98516E-05	0	None	0	0	None	0	0	0	0	0
S/R	None	None	0.497	D	0.609	0.208	0.478680857624	gnomAD-4.0.0	1.59319E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86143E-06	0	0
S/T	rs727503649	None	0.22	N	0.596	0.089	None	gnomAD-4.0.0	6.84592E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65788E-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
S/A	0.0997	likely_benign	0.1048	benign	-0.732	Destabilizing	0.072	N	0.565	neutral	None	None	None	None	N
S/C	0.145	likely_benign	0.1585	benign	-0.629	Destabilizing	0.958	D	0.631	neutral	N	0.505357655	None	None	N
S/D	0.39	ambiguous	0.4364	ambiguous	-0.571	Destabilizing	0.157	N	0.574	neutral	None	None	None	None	N
S/E	0.4832	ambiguous	0.5204	ambiguous	-0.598	Destabilizing	0.272	N	0.597	neutral	None	None	None	None	N
S/F	0.1764	likely_benign	0.1807	benign	-1.091	Destabilizing	0.89	D	0.702	prob.neutral	None	None	None	None	N
S/G	0.1253	likely_benign	0.1367	benign	-0.937	Destabilizing	0.001	N	0.223	neutral	N	0.493240881	None	None	N
S/H	0.3242	likely_benign	0.3452	ambiguous	-1.479	Destabilizing	0.832	D	0.623	neutral	None	None	None	None	N
S/I	0.1854	likely_benign	0.2056	benign	-0.299	Destabilizing	0.667	D	0.699	prob.neutral	N	0.48789851	None	None	N
S/K	0.6693	likely_pathogenic	0.7217	pathogenic	-0.76	Destabilizing	0.157	N	0.611	neutral	None	None	None	None	N
S/L	0.115	likely_benign	0.1216	benign	-0.299	Destabilizing	0.567	D	0.627	neutral	None	None	None	None	N
S/M	0.2008	likely_benign	0.2149	benign	0.087	Stabilizing	0.968	D	0.62	neutral	None	None	None	None	N
S/N	0.1249	likely_benign	0.142	benign	-0.72	Destabilizing	0.001	N	0.314	neutral	N	0.497506842	None	None	N
S/P	0.9456	likely_pathogenic	0.9596	pathogenic	-0.412	Destabilizing	0.726	D	0.614	neutral	None	None	None	None	N
S/Q	0.4603	ambiguous	0.4904	ambiguous	-0.98	Destabilizing	0.567	D	0.617	neutral	None	None	None	None	N
S/R	0.5258	ambiguous	0.5729	pathogenic	-0.57	Destabilizing	0.497	N	0.609	neutral	D	0.529403163	None	None	N
S/T	0.0785	likely_benign	0.0809	benign	-0.74	Destabilizing	0.22	N	0.596	neutral	N	0.469525354	None	None	N
S/V	0.2041	likely_benign	0.2206	benign	-0.412	Destabilizing	0.726	D	0.65	neutral	None	None	None	None	N
S/W	0.3166	likely_benign	0.3248	benign	-1.041	Destabilizing	0.968	D	0.749	deleterious	None	None	None	None	N
S/Y	0.1962	likely_benign	0.2048	benign	-0.772	Destabilizing	0.89	D	0.707	prob.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.