TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2553	7882;7883;7884	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
N2AB	2553	7882;7883;7884	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
N2A	2553	7882;7883;7884	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
N2B	2507	7744;7745;7746	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
Novex-1	2507	7744;7745;7746	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
Novex-2	2507	7744;7745;7746	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032
Novex-3	2553	7882;7883;7884	chr2:178773307;178773306;178773305	chr2:179638034;179638033;179638032

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-15
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2879
• 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	rs367621583	0.33	0.549	D	0.499	0.385	None	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	9.93E-05	0	None	0	None	0	0	0
E/A	rs367621583	0.33	0.549	D	0.499	0.385	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	2.88184E-04	0	None	0	0	0	0	0
E/A	rs367621583	0.33	0.549	D	0.499	0.385	None	gnomAD-4.0.0	2.5618E-06	None	None	None	None	N	None	0	0	None	8.17996E-05	0	None	0	0	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	0.3812	ambiguous	0.341	ambiguous	-0.737	Destabilizing	0.549	D	0.499	neutral	D	0.624557274	None	None	N
E/C	0.9479	likely_pathogenic	0.9437	pathogenic	-0.497	Destabilizing	0.992	D	0.642	neutral	None	None	None	None	N
E/D	0.3662	ambiguous	0.3374	benign	-1.186	Destabilizing	0.004	N	0.328	neutral	D	0.575003209	None	None	N
E/F	0.9494	likely_pathogenic	0.9337	pathogenic	0.04	Stabilizing	0.972	D	0.629	neutral	None	None	None	None	N
E/G	0.5679	likely_pathogenic	0.503	ambiguous	-1.145	Destabilizing	0.549	D	0.519	neutral	D	0.627992015	None	None	N
E/H	0.773	likely_pathogenic	0.7346	pathogenic	-0.224	Destabilizing	0.92	D	0.531	neutral	None	None	None	None	N
E/I	0.685	likely_pathogenic	0.6459	pathogenic	0.391	Stabilizing	0.85	D	0.615	neutral	None	None	None	None	N
E/K	0.4395	ambiguous	0.3588	ambiguous	-0.674	Destabilizing	0.379	N	0.552	neutral	D	0.564832684	None	None	N
E/L	0.7835	likely_pathogenic	0.7483	pathogenic	0.391	Stabilizing	0.617	D	0.582	neutral	None	None	None	None	N
E/M	0.7632	likely_pathogenic	0.7269	pathogenic	0.775	Stabilizing	0.992	D	0.613	neutral	None	None	None	None	N
E/N	0.5762	likely_pathogenic	0.5388	ambiguous	-1.25	Destabilizing	0.021	N	0.454	neutral	None	None	None	None	N
E/P	0.9701	likely_pathogenic	0.968	pathogenic	0.037	Stabilizing	0.92	D	0.573	neutral	None	None	None	None	N
E/Q	0.2919	likely_benign	0.2637	benign	-1.068	Destabilizing	0.549	D	0.53	neutral	D	0.583563682	None	None	N
E/R	0.6375	likely_pathogenic	0.5727	pathogenic	-0.351	Destabilizing	0.012	N	0.421	neutral	None	None	None	None	N
E/S	0.4092	ambiguous	0.3816	ambiguous	-1.597	Destabilizing	0.447	N	0.517	neutral	None	None	None	None	N
E/T	0.4019	ambiguous	0.3643	ambiguous	-1.25	Destabilizing	0.021	N	0.415	neutral	None	None	None	None	N
E/V	0.4638	ambiguous	0.4163	ambiguous	0.037	Stabilizing	0.81	D	0.583	neutral	D	0.599020109	None	None	N
E/W	0.9813	likely_pathogenic	0.9738	pathogenic	0.296	Stabilizing	0.992	D	0.649	neutral	None	None	None	None	N
E/Y	0.912	likely_pathogenic	0.8864	pathogenic	0.302	Stabilizing	0.972	D	0.61	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.