TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24394	73405;73406;73407	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
N2AB	22753	68482;68483;68484	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
N2A	21826	65701;65702;65703	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
N2B	15329	46210;46211;46212	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
Novex-1	15454	46585;46586;46587	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
Novex-2	15521	46786;46787;46788	chr2:178572952;178572951;178572950	chr2:179437679;179437678;179437677
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-65
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.4362
• 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/D	rs750460710	-1.259	0.434	N	0.221	0.117	0.254761474806	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.66445E-04
E/D	rs750460710	-1.259	0.434	N	0.221	0.117	0.254761474806	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs750460710	-1.259	0.434	N	0.221	0.117	0.254761474806	gnomAD-4.0.0	7.43885E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01733E-05	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	0.121	likely_benign	0.1258	benign	-0.916	Destabilizing	0.998	D	0.667	neutral	N	0.48211966	None	None	N
E/C	0.769	likely_pathogenic	0.7854	pathogenic	-0.491	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/D	0.1408	likely_benign	0.1645	benign	-1.091	Destabilizing	0.434	N	0.221	neutral	N	0.480131424	None	None	N
E/F	0.7259	likely_pathogenic	0.7469	pathogenic	-0.205	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.1819	likely_benign	0.1911	benign	-1.308	Destabilizing	0.999	D	0.753	deleterious	N	0.501807304	None	None	N
E/H	0.4777	ambiguous	0.4983	ambiguous	-0.401	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/I	0.2716	likely_benign	0.286	benign	0.164	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/K	0.2076	likely_benign	0.2122	benign	-0.672	Destabilizing	0.998	D	0.548	neutral	N	0.507109802	None	None	N
E/L	0.3374	likely_benign	0.3652	ambiguous	0.164	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/M	0.3618	ambiguous	0.3831	ambiguous	0.622	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/N	0.2237	likely_benign	0.2601	benign	-1.214	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.354	ambiguous	0.381	ambiguous	-0.175	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
E/Q	0.1413	likely_benign	0.1403	benign	-1.054	Destabilizing	0.999	D	0.663	neutral	N	0.515614642	None	None	N
E/R	0.3508	ambiguous	0.3615	ambiguous	-0.319	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/S	0.1834	likely_benign	0.199	benign	-1.564	Destabilizing	0.997	D	0.594	neutral	None	None	None	None	N
E/T	0.175	likely_benign	0.1832	benign	-1.234	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.1716	likely_benign	0.1748	benign	-0.175	Destabilizing	1.0	D	0.787	deleterious	N	0.481652361	None	None	N
E/W	0.901	likely_pathogenic	0.9067	pathogenic	0.088	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/Y	0.5954	likely_pathogenic	0.6229	pathogenic	0.063	Stabilizing	1.0	D	0.783	deleterious	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.