TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18448	55567;55568;55569	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
N2AB	16807	50644;50645;50646	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
N2A	15880	47863;47864;47865	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
N2B	9383	28372;28373;28374	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
Novex-1	9508	28747;28748;28749	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
Novex-2	9575	28948;28949;28950	chr2:178601748;178601747;178601746	chr2:179466475;179466474;179466473
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-115
• Domain position: 67
• Structural Position: 143
• Q(SASA): 0.3997
• 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
E/A	rs1297622212	-0.442	0.09	N	0.341	0.086	0.203808441222	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	6.51E-05	0	None	0	0	None	0	None	0	0	0
E/A	rs1297622212	-0.442	0.09	N	0.341	0.086	0.203808441222	gnomAD-4.0.0	1.37305E-06	None	None	None	None	N	None	3.01896E-05	0	None	0	0	None	0	0	9.00679E-07	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
E/A	0.1086	likely_benign	0.0943	benign	-0.462	Destabilizing	0.09	N	0.341	neutral	N	0.470119134	None	None	N
E/C	0.6901	likely_pathogenic	0.5949	pathogenic	-0.036	Destabilizing	0.981	D	0.431	neutral	None	None	None	None	N
E/D	0.088	likely_benign	0.0801	benign	-0.379	Destabilizing	0.001	N	0.107	neutral	N	0.408606528	None	None	N
E/F	0.5221	ambiguous	0.4545	ambiguous	-0.39	Destabilizing	0.818	D	0.434	neutral	None	None	None	None	N
E/G	0.1529	likely_benign	0.1276	benign	-0.672	Destabilizing	0.193	N	0.369	neutral	N	0.469599059	None	None	N
E/H	0.2954	likely_benign	0.2408	benign	-0.283	Destabilizing	0.818	D	0.383	neutral	None	None	None	None	N
E/I	0.2102	likely_benign	0.1765	benign	0.058	Stabilizing	0.241	N	0.417	neutral	None	None	None	None	N
E/K	0.1377	likely_benign	0.1193	benign	0.164	Stabilizing	0.324	N	0.267	neutral	N	0.423845339	None	None	N
E/L	0.2841	likely_benign	0.2175	benign	0.058	Stabilizing	0.241	N	0.409	neutral	None	None	None	None	N
E/M	0.3347	likely_benign	0.2773	benign	0.253	Stabilizing	0.818	D	0.393	neutral	None	None	None	None	N
E/N	0.1337	likely_benign	0.1042	benign	-0.08	Destabilizing	0.002	N	0.237	neutral	None	None	None	None	N
E/P	0.6739	likely_pathogenic	0.6101	pathogenic	-0.095	Destabilizing	0.818	D	0.416	neutral	None	None	None	None	N
E/Q	0.1128	likely_benign	0.0964	benign	-0.042	Destabilizing	0.324	N	0.351	neutral	N	0.448474425	None	None	N
E/R	0.2156	likely_benign	0.1851	benign	0.342	Stabilizing	0.69	D	0.347	neutral	None	None	None	None	N
E/S	0.128	likely_benign	0.1037	benign	-0.271	Destabilizing	0.116	N	0.264	neutral	None	None	None	None	N
E/T	0.132	likely_benign	0.1089	benign	-0.104	Destabilizing	0.008	N	0.19	neutral	None	None	None	None	N
E/V	0.129	likely_benign	0.1128	benign	-0.095	Destabilizing	0.003	N	0.203	neutral	N	0.435430557	None	None	N
E/W	0.7997	likely_pathogenic	0.7557	pathogenic	-0.254	Destabilizing	0.981	D	0.511	neutral	None	None	None	None	N
E/Y	0.3955	ambiguous	0.3392	benign	-0.159	Destabilizing	0.932	D	0.408	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.