TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4907	14944;14945;14946	chr2:178735727;178735726;178735725	chr2:179600454;179600453;179600452
N2AB	4590	13993;13994;13995	chr2:178735727;178735726;178735725	chr2:179600454;179600453;179600452
N2A	3663	11212;11213;11214	chr2:178735727;178735726;178735725	chr2:179600454;179600453;179600452
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-32
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1343
• 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
L/F	None	None	1.0	N	0.798	0.437	0.499793596984	gnomAD-4.0.0	6.84227E-07	None	None	None	None	N	None	0	0	None	0	2.52207E-05	None	0	0	0	0	0
L/I	rs2081327474	None	0.999	D	0.591	0.48	0.498641525541	gnomAD-4.0.0	6.84227E-07	None	None	None	None	N	None	0	0	None	0	2.52207E-05	None	0	0	0	0	0
L/P	None	None	1.0	D	0.905	0.842	0.907507965639	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
L/A	0.6988	likely_pathogenic	0.7461	pathogenic	-2.612	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
L/C	0.732	likely_pathogenic	0.7736	pathogenic	-1.914	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/D	0.9952	likely_pathogenic	0.9965	pathogenic	-3.411	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.9617	likely_pathogenic	0.9711	pathogenic	-3.138	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/F	0.1354	likely_benign	0.1522	benign	-1.669	Destabilizing	1.0	D	0.798	deleterious	N	0.39908953	None	None	N
L/G	0.9344	likely_pathogenic	0.9479	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/H	0.8513	likely_pathogenic	0.8833	pathogenic	-2.668	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.730703279	None	None	N
L/I	0.1221	likely_benign	0.1319	benign	-1.028	Destabilizing	0.999	D	0.591	neutral	D	0.563570563	None	None	N
L/K	0.9259	likely_pathogenic	0.9428	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/M	0.1335	likely_benign	0.1454	benign	-1.058	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
L/N	0.9752	likely_pathogenic	0.9813	pathogenic	-2.657	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.9843	likely_pathogenic	0.9893	pathogenic	-1.546	Destabilizing	1.0	D	0.905	deleterious	D	0.788986181	None	None	N
L/Q	0.8335	likely_pathogenic	0.8634	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/R	0.8493	likely_pathogenic	0.8762	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.788986181	None	None	N
L/S	0.905	likely_pathogenic	0.924	pathogenic	-3.214	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/T	0.7431	likely_pathogenic	0.7922	pathogenic	-2.791	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/V	0.1407	likely_benign	0.1562	benign	-1.546	Destabilizing	0.999	D	0.615	neutral	D	0.679074332	None	None	N
L/W	0.5001	ambiguous	0.5442	ambiguous	-2.038	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/Y	0.6737	likely_pathogenic	0.7282	pathogenic	-1.771	Destabilizing	1.0	D	0.841	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.