TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30727	92404;92405;92406	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
N2AB	29086	87481;87482;87483	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
N2A	28159	84700;84701;84702	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
N2B	21662	65209;65210;65211	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
Novex-1	21787	65584;65585;65586	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
Novex-2	21854	65785;65786;65787	chr2:178549447;178549446;178549445	chr2:179414174;179414173;179414172
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: Fn3-112
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5604
• 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	None	None	0.896	N	0.634	0.405	0.431931272081	gnomAD-4.0.0	6.87049E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03045E-07	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	0.1988	likely_benign	0.2232	benign	-0.562	Destabilizing	0.896	D	0.634	neutral	N	0.493334153	None	None	N
E/C	0.793	likely_pathogenic	0.8236	pathogenic	-0.155	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
E/D	0.1439	likely_benign	0.1825	benign	-0.705	Destabilizing	0.004	N	0.23	neutral	N	0.483712595	None	None	N
E/F	0.6791	likely_pathogenic	0.7474	pathogenic	-0.26	Destabilizing	0.996	D	0.804	deleterious	None	None	None	None	N
E/G	0.2623	likely_benign	0.3011	benign	-0.842	Destabilizing	0.896	D	0.654	neutral	N	0.488334177	None	None	N
E/H	0.4676	ambiguous	0.5121	ambiguous	-0.335	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
E/I	0.2406	likely_benign	0.2817	benign	0.171	Stabilizing	0.988	D	0.807	deleterious	None	None	None	None	N
E/K	0.188	likely_benign	0.2006	benign	0.021	Stabilizing	0.896	D	0.579	neutral	N	0.48717446	None	None	N
E/L	0.3339	likely_benign	0.3758	ambiguous	0.171	Stabilizing	0.988	D	0.771	deleterious	None	None	None	None	N
E/M	0.3775	ambiguous	0.4425	ambiguous	0.401	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
E/N	0.2556	likely_benign	0.3269	benign	-0.399	Destabilizing	0.851	D	0.568	neutral	None	None	None	None	N
E/P	0.936	likely_pathogenic	0.951	pathogenic	-0.052	Destabilizing	0.988	D	0.711	prob.delet.	None	None	None	None	N
E/Q	0.1378	likely_benign	0.1438	benign	-0.325	Destabilizing	0.946	D	0.581	neutral	N	0.466707522	None	None	N
E/R	0.3132	likely_benign	0.3369	benign	0.223	Stabilizing	0.988	D	0.599	neutral	None	None	None	None	N
E/S	0.2138	likely_benign	0.2564	benign	-0.592	Destabilizing	0.919	D	0.573	neutral	None	None	None	None	N
E/T	0.2046	likely_benign	0.2423	benign	-0.363	Destabilizing	0.959	D	0.668	neutral	None	None	None	None	N
E/V	0.1596	likely_benign	0.1758	benign	-0.052	Destabilizing	0.984	D	0.7	prob.neutral	N	0.465265945	None	None	N
E/W	0.8965	likely_pathogenic	0.9216	pathogenic	-0.053	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/Y	0.5823	likely_pathogenic	0.6282	pathogenic	-0.003	Destabilizing	0.996	D	0.794	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.