TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23466	70621;70622;70623	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
N2AB	21825	65698;65699;65700	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
N2A	20898	62917;62918;62919	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
N2B	14401	43426;43427;43428	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
Novex-1	14526	43801;43802;43803	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
Novex-2	14593	44002;44003;44004	chr2:178575736;178575735;178575734	chr2:179440463;179440462;179440461
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-58
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.86
• 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
R/C	rs749744742	-0.049	0.996	N	0.443	0.4	0.34854441366	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	4.13E-05	0	None	0	0	None	0	None	0	1.56E-05	0
R/C	rs749744742	-0.049	0.996	N	0.443	0.4	0.34854441366	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.42E-05	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs749744742	-0.049	0.996	N	0.443	0.4	0.34854441366	gnomAD-4.0.0	8.67778E-06	None	None	None	None	I	None	1.33618E-05	1.66756E-05	None	0	0	None	0	0	1.01727E-05	0	0
R/G	None	None	0.579	N	0.54	0.278	0.272639205421	gnomAD-4.0.0	6.84309E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99565E-07	0	0
R/H	rs1193026411	-0.582	0.009	N	0.303	0.122	0.18274738541	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	1.65837E-04
R/H	rs1193026411	-0.582	0.009	N	0.303	0.122	0.18274738541	gnomAD-4.0.0	1.0949E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.07949E-05	2.31895E-05	3.31389E-05
R/P	None	None	0.004	N	0.291	0.266	0.12205267543	gnomAD-4.0.0	6.84315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99572E-07	0	0
R/S	rs749744742	None	0.579	N	0.497	0.233	0.223146558224	gnomAD-4.0.0	1.36862E-06	None	None	None	None	I	None	2.98882E-05	0	None	0	0	None	0	1.73551E-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
R/A	0.5963	likely_pathogenic	0.5881	pathogenic	0.04	Stabilizing	0.129	N	0.481	neutral	None	None	None	None	I
R/C	0.3573	ambiguous	0.3555	ambiguous	-0.207	Destabilizing	0.996	D	0.443	neutral	N	0.472774363	None	None	I
R/D	0.8533	likely_pathogenic	0.8295	pathogenic	-0.254	Destabilizing	0.418	N	0.555	neutral	None	None	None	None	I
R/E	0.6423	likely_pathogenic	0.616	pathogenic	-0.212	Destabilizing	0.228	N	0.427	neutral	None	None	None	None	I
R/F	0.8135	likely_pathogenic	0.8235	pathogenic	-0.279	Destabilizing	0.716	D	0.491	neutral	None	None	None	None	I
R/G	0.5574	ambiguous	0.5435	ambiguous	-0.105	Destabilizing	0.579	D	0.54	neutral	N	0.468167412	None	None	I
R/H	0.183	likely_benign	0.1709	benign	-0.608	Destabilizing	0.009	N	0.303	neutral	N	0.452005881	None	None	I
R/I	0.546	ambiguous	0.5716	pathogenic	0.376	Stabilizing	0.264	N	0.551	neutral	None	None	None	None	I
R/K	0.1362	likely_benign	0.1287	benign	-0.126	Destabilizing	0.004	N	0.129	neutral	None	None	None	None	I
R/L	0.4957	ambiguous	0.4898	ambiguous	0.376	Stabilizing	0.221	N	0.529	neutral	N	0.483059506	None	None	I
R/M	0.5738	likely_pathogenic	0.5878	pathogenic	-0.041	Destabilizing	0.836	D	0.489	neutral	None	None	None	None	I
R/N	0.7728	likely_pathogenic	0.7658	pathogenic	-0.011	Destabilizing	0.264	N	0.437	neutral	None	None	None	None	I
R/P	0.467	ambiguous	0.4547	ambiguous	0.283	Stabilizing	0.004	N	0.291	neutral	N	0.327327231	None	None	I
R/Q	0.1908	likely_benign	0.1831	benign	-0.062	Destabilizing	0.418	N	0.466	neutral	None	None	None	None	I
R/S	0.7487	likely_pathogenic	0.7329	pathogenic	-0.218	Destabilizing	0.579	D	0.497	neutral	N	0.459758572	None	None	I
R/T	0.5506	ambiguous	0.5436	ambiguous	-0.066	Destabilizing	0.418	N	0.505	neutral	None	None	None	None	I
R/V	0.5735	likely_pathogenic	0.5782	pathogenic	0.283	Stabilizing	0.002	N	0.29	neutral	None	None	None	None	I
R/W	0.4494	ambiguous	0.4504	ambiguous	-0.449	Destabilizing	0.983	D	0.463	neutral	None	None	None	None	I
R/Y	0.6501	likely_pathogenic	0.6439	pathogenic	-0.036	Destabilizing	0.557	D	0.5	neutral	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.