TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20533	61822;61823;61824	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
N2AB	18892	56899;56900;56901	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
N2A	17965	54118;54119;54120	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
N2B	11468	34627;34628;34629	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
Novex-1	11593	35002;35003;35004	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
Novex-2	11660	35203;35204;35205	chr2:178590128;178590127;178590126	chr2:179454855;179454854;179454853
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-121
• Domain position: 55
• Structural Position: 137
• Q(SASA): 0.247
• 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	rs970448292	-1.269	0.669	N	0.51	0.278	0.251116650651	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs970448292	-1.269	0.669	N	0.51	0.278	0.251116650651	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs970448292	-1.269	0.669	N	0.51	0.278	0.251116650651	gnomAD-4.0.0	1.23986E-06	None	None	None	None	N	None	2.67187E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs970448292	None	0.136	N	0.386	0.252	0.20549828249	gnomAD-4.0.0	1.36886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9968E-07	0	1.657E-05

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	0.3015	likely_benign	0.3372	benign	-0.889	Destabilizing	0.454	N	0.458	neutral	N	0.479763777	None	None	N
E/C	0.8799	likely_pathogenic	0.881	pathogenic	-0.577	Destabilizing	0.998	D	0.658	neutral	None	None	None	None	N
E/D	0.3465	ambiguous	0.3739	ambiguous	-1.679	Destabilizing	0.012	N	0.201	neutral	N	0.514492426	None	None	N
E/F	0.8457	likely_pathogenic	0.8638	pathogenic	-0.35	Destabilizing	0.974	D	0.639	neutral	None	None	None	None	N
E/G	0.4784	ambiguous	0.5441	ambiguous	-1.336	Destabilizing	0.012	N	0.4	neutral	N	0.493117076	None	None	N
E/H	0.6529	likely_pathogenic	0.698	pathogenic	-0.619	Destabilizing	0.016	N	0.241	neutral	None	None	None	None	N
E/I	0.5333	ambiguous	0.5443	ambiguous	0.373	Stabilizing	0.974	D	0.615	neutral	None	None	None	None	N
E/K	0.5587	ambiguous	0.6416	pathogenic	-1.301	Destabilizing	0.669	D	0.51	neutral	N	0.487959186	None	None	N
E/L	0.6494	likely_pathogenic	0.6762	pathogenic	0.373	Stabilizing	0.842	D	0.583	neutral	None	None	None	None	N
E/M	0.626	likely_pathogenic	0.6429	pathogenic	1.003	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	N
E/N	0.5619	ambiguous	0.6297	pathogenic	-1.701	Destabilizing	0.728	D	0.483	neutral	None	None	None	None	N
E/P	0.9892	likely_pathogenic	0.9893	pathogenic	-0.028	Destabilizing	0.974	D	0.536	neutral	None	None	None	None	N
E/Q	0.2431	likely_benign	0.2951	benign	-1.386	Destabilizing	0.136	N	0.386	neutral	N	0.455790839	None	None	N
E/R	0.6444	likely_pathogenic	0.7212	pathogenic	-1.135	Destabilizing	0.842	D	0.511	neutral	None	None	None	None	N
E/S	0.3424	ambiguous	0.3846	ambiguous	-2.242	Highly Destabilizing	0.688	D	0.471	neutral	None	None	None	None	N
E/T	0.4028	ambiguous	0.4448	ambiguous	-1.843	Destabilizing	0.915	D	0.499	neutral	None	None	None	None	N
E/V	0.3502	ambiguous	0.3705	ambiguous	-0.028	Destabilizing	0.891	D	0.594	neutral	N	0.462775527	None	None	N
E/W	0.9545	likely_pathogenic	0.9592	pathogenic	-0.405	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
E/Y	0.7927	likely_pathogenic	0.8129	pathogenic	-0.169	Destabilizing	0.949	D	0.597	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.