TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13701	41326;41327;41328	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
N2AB	12060	36403;36404;36405	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
N2A	11133	33622;33623;33624	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
N2B	4636	14131;14132;14133	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
Novex-1	4761	14506;14507;14508	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
Novex-2	4828	14707;14708;14709	chr2:178636626;178636625;178636624	chr2:179501353;179501352;179501351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-87
• Domain position: 18
• Structural Position: 24
• Q(SASA): 0.3839
• Predicted PPI site: I

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
G/A	None	None	1.0	D	0.766	0.879	0.661428323319	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43287E-05	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
G/A	0.4515	ambiguous	0.6288	pathogenic	-0.194	Destabilizing	1.0	D	0.766	deleterious	D	0.719779615	None	None	I
G/C	0.8009	likely_pathogenic	0.89	pathogenic	-0.873	Destabilizing	1.0	D	0.821	deleterious	D	0.776535402	None	None	I
G/D	0.736	likely_pathogenic	0.8715	pathogenic	-0.323	Destabilizing	1.0	D	0.841	deleterious	D	0.634096156	None	None	I
G/E	0.7752	likely_pathogenic	0.8989	pathogenic	-0.487	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/F	0.9497	likely_pathogenic	0.9751	pathogenic	-0.957	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
G/H	0.9051	likely_pathogenic	0.9589	pathogenic	-0.404	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/I	0.9025	likely_pathogenic	0.9485	pathogenic	-0.396	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/K	0.9176	likely_pathogenic	0.9655	pathogenic	-0.574	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/L	0.909	likely_pathogenic	0.9552	pathogenic	-0.396	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/M	0.9429	likely_pathogenic	0.9729	pathogenic	-0.421	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/N	0.7185	likely_pathogenic	0.8571	pathogenic	-0.298	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/P	0.9528	likely_pathogenic	0.9777	pathogenic	-0.298	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
G/Q	0.8451	likely_pathogenic	0.9307	pathogenic	-0.567	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.8447	likely_pathogenic	0.9284	pathogenic	-0.191	Destabilizing	1.0	D	0.862	deleterious	D	0.661058181	None	None	I
G/S	0.3262	likely_benign	0.4957	ambiguous	-0.463	Destabilizing	1.0	D	0.813	deleterious	D	0.632981635	None	None	I
G/T	0.6402	likely_pathogenic	0.7881	pathogenic	-0.553	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/V	0.7933	likely_pathogenic	0.8867	pathogenic	-0.298	Destabilizing	1.0	D	0.811	deleterious	D	0.776779228	None	None	I
G/W	0.9332	likely_pathogenic	0.9671	pathogenic	-1.088	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/Y	0.93	likely_pathogenic	0.9683	pathogenic	-0.737	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I

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.