TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21409	64450;64451;64452	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
N2AB	19768	59527;59528;59529	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
N2A	18841	56746;56747;56748	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
N2B	12344	37255;37256;37257	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
Novex-1	12469	37630;37631;37632	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
Novex-2	12536	37831;37832;37833	chr2:178586676;178586675;178586674	chr2:179451403;179451402;179451401
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: Fn3-43
• Domain position: 44
• Structural Position: 51
• Q(SASA): 0.3207
• 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/K	None	None	0.055	N	0.213	0.199	0.229264304666	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

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	0.1272	likely_benign	0.108	benign	-0.189	Destabilizing	0.012	N	0.33	neutral	N	0.454566183	None	None	N
E/C	0.687	likely_pathogenic	0.6081	pathogenic	-0.11	Destabilizing	0.864	D	0.377	neutral	None	None	None	None	N
E/D	0.0556	likely_benign	0.0557	benign	-0.23	Destabilizing	None	N	0.083	neutral	N	0.433553406	None	None	N
E/F	0.6373	likely_pathogenic	0.5418	ambiguous	-0.143	Destabilizing	0.628	D	0.39	neutral	None	None	None	None	N
E/G	0.0735	likely_benign	0.0624	benign	-0.358	Destabilizing	None	N	0.199	neutral	N	0.360325084	None	None	N
E/H	0.3878	ambiguous	0.3085	benign	0.242	Stabilizing	0.356	N	0.268	neutral	None	None	None	None	N
E/I	0.3097	likely_benign	0.2562	benign	0.21	Stabilizing	0.356	N	0.401	neutral	None	None	None	None	N
E/K	0.2346	likely_benign	0.1788	benign	0.301	Stabilizing	0.055	N	0.213	neutral	N	0.426032788	None	None	N
E/L	0.3118	likely_benign	0.2519	benign	0.21	Stabilizing	0.072	N	0.375	neutral	None	None	None	None	N
E/M	0.4066	ambiguous	0.3438	ambiguous	0.116	Stabilizing	0.864	D	0.345	neutral	None	None	None	None	N
E/N	0.1161	likely_benign	0.1023	benign	0.126	Stabilizing	0.038	N	0.185	neutral	None	None	None	None	N
E/P	0.4906	ambiguous	0.3999	ambiguous	0.097	Stabilizing	0.136	N	0.318	neutral	None	None	None	None	N
E/Q	0.1749	likely_benign	0.1491	benign	0.141	Stabilizing	0.055	N	0.291	neutral	N	0.47488274	None	None	N
E/R	0.376	ambiguous	0.2921	benign	0.553	Stabilizing	0.072	N	0.282	neutral	None	None	None	None	N
E/S	0.1156	likely_benign	0.1004	benign	-0.07	Destabilizing	0.016	N	0.244	neutral	None	None	None	None	N
E/T	0.1439	likely_benign	0.1255	benign	0.063	Stabilizing	0.072	N	0.293	neutral	None	None	None	None	N
E/V	0.2052	likely_benign	0.1709	benign	0.097	Stabilizing	0.106	N	0.377	neutral	N	0.467938125	None	None	N
E/W	0.8115	likely_pathogenic	0.7509	pathogenic	-0.047	Destabilizing	0.864	D	0.405	neutral	None	None	None	None	N
E/Y	0.4576	ambiguous	0.3874	ambiguous	0.09	Stabilizing	0.628	D	0.371	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.