TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15095	45508;45509;45510	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
N2AB	13454	40585;40586;40587	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
N2A	12527	37804;37805;37806	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
N2B	6030	18313;18314;18315	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
Novex-1	6155	18688;18689;18690	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
Novex-2	6222	18889;18890;18891	chr2:178621541;178621540;178621539	chr2:179486268;179486267;179486266
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-102
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.5621
• 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	rs2154212024	None	0.684	D	0.289	0.433	0.394536629495	gnomAD-4.0.0	1.59392E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43328E-05	0
E/Q	None	None	0.815	D	0.323	0.413	0.399740851666	gnomAD-4.0.0	1.59392E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41779E-04	0	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	0.1392	likely_benign	0.1657	benign	-0.575	Destabilizing	0.028	N	0.194	neutral	N	0.502326748	None	None	N
E/C	0.8613	likely_pathogenic	0.9189	pathogenic	-0.223	Destabilizing	0.996	D	0.335	neutral	None	None	None	None	N
E/D	0.1278	likely_benign	0.1432	benign	-0.395	Destabilizing	0.003	N	0.154	neutral	N	0.503139509	None	None	N
E/F	0.7795	likely_pathogenic	0.8433	pathogenic	-0.384	Destabilizing	0.984	D	0.333	neutral	None	None	None	None	N
E/G	0.1372	likely_benign	0.1674	benign	-0.806	Destabilizing	0.472	N	0.338	neutral	D	0.578026506	None	None	N
E/H	0.4747	ambiguous	0.5653	pathogenic	-0.268	Destabilizing	0.984	D	0.295	neutral	None	None	None	None	N
E/I	0.4291	ambiguous	0.506	ambiguous	0.016	Stabilizing	0.953	D	0.351	neutral	None	None	None	None	N
E/K	0.1566	likely_benign	0.1975	benign	-0.183	Destabilizing	0.684	D	0.289	neutral	D	0.545195273	None	None	N
E/L	0.4454	ambiguous	0.532	ambiguous	0.016	Stabilizing	0.742	D	0.354	neutral	None	None	None	None	N
E/M	0.5199	ambiguous	0.6041	pathogenic	0.194	Stabilizing	0.996	D	0.321	neutral	None	None	None	None	N
E/N	0.2607	likely_benign	0.3191	benign	-0.354	Destabilizing	0.59	D	0.272	neutral	None	None	None	None	N
E/P	0.5707	likely_pathogenic	0.6641	pathogenic	-0.161	Destabilizing	0.953	D	0.297	neutral	None	None	None	None	N
E/Q	0.1479	likely_benign	0.1751	benign	-0.302	Destabilizing	0.815	D	0.323	neutral	D	0.544016735	None	None	N
E/R	0.2525	likely_benign	0.3112	benign	0.113	Stabilizing	0.953	D	0.263	neutral	None	None	None	None	N
E/S	0.1724	likely_benign	0.216	benign	-0.603	Destabilizing	0.101	N	0.179	neutral	None	None	None	None	N
E/T	0.2256	likely_benign	0.2845	benign	-0.426	Destabilizing	0.59	D	0.343	neutral	None	None	None	None	N
E/V	0.2563	likely_benign	0.3089	benign	-0.161	Destabilizing	0.684	D	0.349	neutral	D	0.624352036	None	None	N
E/W	0.8706	likely_pathogenic	0.9132	pathogenic	-0.227	Destabilizing	0.996	D	0.467	neutral	None	None	None	None	N
E/Y	0.6701	likely_pathogenic	0.753	pathogenic	-0.169	Destabilizing	0.984	D	0.328	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.