TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22250	66973;66974;66975	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
N2AB	20609	62050;62051;62052	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
N2A	19682	59269;59270;59271	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
N2B	13185	39778;39779;39780	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
Novex-1	13310	40153;40154;40155	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
Novex-2	13377	40354;40355;40356	chr2:178581520;178581519;178581518	chr2:179446247;179446246;179446245
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-49
• Domain position: 95
• Structural Position: 127
• Q(SASA): 0.3371
• 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
H/Q	rs928913814	-1.614	0.999	D	0.775	0.233	0.497741790239	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
H/Q	rs928913814	-1.614	0.999	D	0.775	0.233	0.497741790239	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/Q	rs928913814	-1.614	0.999	D	0.775	0.233	0.497741790239	gnomAD-4.0.0	4.99094E-06	None	None	None	None	N	None	1.33815E-05	0	None	0	0	None	0	0	5.96897E-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
H/A	0.4609	ambiguous	0.4048	ambiguous	-2.08	Highly Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
H/C	0.1709	likely_benign	0.1509	benign	-1.057	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
H/D	0.7121	likely_pathogenic	0.6946	pathogenic	-2.11	Highly Destabilizing	0.999	D	0.795	deleterious	D	0.530397667	None	None	N
H/E	0.6046	likely_pathogenic	0.5504	ambiguous	-1.908	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
H/F	0.3074	likely_benign	0.2807	benign	-0.06	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
H/G	0.7084	likely_pathogenic	0.6762	pathogenic	-2.513	Highly Destabilizing	0.998	D	0.737	deleterious	None	None	None	None	N
H/I	0.19	likely_benign	0.1595	benign	-0.783	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
H/K	0.564	ambiguous	0.5101	ambiguous	-1.261	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
H/L	0.1691	likely_benign	0.1554	benign	-0.783	Destabilizing	0.999	D	0.804	deleterious	D	0.530224309	None	None	N
H/M	0.5093	ambiguous	0.4634	ambiguous	-0.899	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
H/N	0.23	likely_benign	0.2191	benign	-2.032	Highly Destabilizing	0.997	D	0.611	neutral	D	0.530397667	None	None	N
H/P	0.4423	ambiguous	0.4085	ambiguous	-1.209	Destabilizing	0.999	D	0.84	deleterious	D	0.530917742	None	None	N
H/Q	0.3952	ambiguous	0.3573	ambiguous	-1.691	Destabilizing	0.999	D	0.775	deleterious	D	0.529530876	None	None	N
H/R	0.3278	likely_benign	0.2946	benign	-1.48	Destabilizing	0.999	D	0.765	deleterious	N	0.500517477	None	None	N
H/S	0.445	ambiguous	0.411	ambiguous	-2.113	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
H/T	0.3423	ambiguous	0.3055	benign	-1.785	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
H/V	0.1638	likely_benign	0.1359	benign	-1.209	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
H/W	0.5098	ambiguous	0.4954	ambiguous	0.652	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
H/Y	0.1008	likely_benign	0.097	benign	0.331	Stabilizing	0.997	D	0.629	neutral	N	0.501730986	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.