TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25801	77626;77627;77628	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
N2AB	24160	72703;72704;72705	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
N2A	23233	69922;69923;69924	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
N2B	16736	50431;50432;50433	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
Novex-1	16861	50806;50807;50808	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
Novex-2	16928	51007;51008;51009	chr2:178568731;178568730;178568729	chr2:179433458;179433457;179433456
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-136
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4802
• 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
K/T	None	None	0.117	N	0.339	0.063	0.235038932564	gnomAD-4.0.0	1.5926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43373E-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
K/A	0.35	ambiguous	0.3829	ambiguous	-0.049	Destabilizing	0.067	N	0.359	neutral	None	None	None	None	N
K/C	0.4245	ambiguous	0.4824	ambiguous	-0.288	Destabilizing	0.935	D	0.357	neutral	None	None	None	None	N
K/D	0.5995	likely_pathogenic	0.6379	pathogenic	-0.098	Destabilizing	0.149	N	0.351	neutral	None	None	None	None	N
K/E	0.2236	likely_benign	0.2409	benign	-0.048	Destabilizing	0.027	N	0.376	neutral	N	0.506136728	None	None	N
K/F	0.5961	likely_pathogenic	0.6329	pathogenic	-0.009	Destabilizing	0.555	D	0.342	neutral	None	None	None	None	N
K/G	0.45	ambiguous	0.494	ambiguous	-0.316	Destabilizing	0.149	N	0.358	neutral	None	None	None	None	N
K/H	0.1692	likely_benign	0.1908	benign	-0.569	Destabilizing	0.555	D	0.349	neutral	None	None	None	None	N
K/I	0.2544	likely_benign	0.2732	benign	0.597	Stabilizing	0.484	N	0.357	neutral	N	0.504984722	None	None	N
K/L	0.2664	likely_benign	0.2898	benign	0.597	Stabilizing	0.149	N	0.358	neutral	None	None	None	None	N
K/M	0.2154	likely_benign	0.2264	benign	0.195	Stabilizing	0.791	D	0.353	neutral	None	None	None	None	N
K/N	0.3993	ambiguous	0.4006	ambiguous	-0.038	Destabilizing	0.117	N	0.33	neutral	N	0.4780161	None	None	N
K/P	0.7451	likely_pathogenic	0.7733	pathogenic	0.411	Stabilizing	0.555	D	0.377	neutral	None	None	None	None	N
K/Q	0.1095	likely_benign	0.1144	benign	-0.122	Destabilizing	0.062	N	0.347	neutral	N	0.496133165	None	None	N
K/R	0.0627	likely_benign	0.0647	benign	-0.261	Destabilizing	None	N	0.151	neutral	N	0.415093436	None	None	N
K/S	0.3871	ambiguous	0.4236	ambiguous	-0.48	Destabilizing	0.149	N	0.327	neutral	None	None	None	None	N
K/T	0.1747	likely_benign	0.1894	benign	-0.264	Destabilizing	0.117	N	0.339	neutral	N	0.493978294	None	None	N
K/V	0.2482	likely_benign	0.275	benign	0.411	Stabilizing	0.149	N	0.349	neutral	None	None	None	None	N
K/W	0.4752	ambiguous	0.5267	ambiguous	-0.03	Destabilizing	0.935	D	0.419	neutral	None	None	None	None	N
K/Y	0.4476	ambiguous	0.478	ambiguous	0.29	Stabilizing	0.555	D	0.346	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.