TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22489	67690;67691;67692	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
N2AB	20848	62767;62768;62769	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
N2A	19921	59986;59987;59988	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
N2B	13424	40495;40496;40497	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
Novex-1	13549	40870;40871;40872	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
Novex-2	13616	41071;41072;41073	chr2:178579732;178579731;178579730	chr2:179444459;179444458;179444457
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-51
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.13
• 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
D/H	None	None	0.998	N	0.753	0.426	0.359963025489	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88288E-05	0	0	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
D/A	0.5288	ambiguous	0.446	ambiguous	-1.943	Destabilizing	0.939	D	0.701	prob.neutral	N	0.508397881	None	None	N
D/C	0.869	likely_pathogenic	0.8283	pathogenic	-0.87	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
D/E	0.3119	likely_benign	0.2688	benign	-0.914	Destabilizing	0.02	N	0.359	neutral	N	0.329252815	None	None	N
D/F	0.9144	likely_pathogenic	0.8825	pathogenic	-1.762	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
D/G	0.6287	likely_pathogenic	0.5747	pathogenic	-2.294	Highly Destabilizing	0.939	D	0.705	prob.neutral	N	0.509611389	None	None	N
D/H	0.5968	likely_pathogenic	0.5385	ambiguous	-1.482	Destabilizing	0.998	D	0.753	deleterious	N	0.495354013	None	None	N
D/I	0.8903	likely_pathogenic	0.8409	pathogenic	-0.942	Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	N
D/K	0.8816	likely_pathogenic	0.862	pathogenic	-1.627	Destabilizing	0.91	D	0.685	prob.neutral	None	None	None	None	N
D/L	0.8273	likely_pathogenic	0.7765	pathogenic	-0.942	Destabilizing	0.986	D	0.773	deleterious	None	None	None	None	N
D/M	0.9357	likely_pathogenic	0.9027	pathogenic	-0.186	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
D/N	0.3127	likely_benign	0.2812	benign	-1.669	Destabilizing	0.939	D	0.708	prob.delet.	N	0.486542529	None	None	N
D/P	0.9968	likely_pathogenic	0.9966	pathogenic	-1.262	Destabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
D/Q	0.7009	likely_pathogenic	0.6372	pathogenic	-1.391	Destabilizing	0.973	D	0.754	deleterious	None	None	None	None	N
D/R	0.8728	likely_pathogenic	0.852	pathogenic	-1.471	Destabilizing	0.986	D	0.714	prob.delet.	None	None	None	None	N
D/S	0.3231	likely_benign	0.2828	benign	-2.38	Highly Destabilizing	0.953	D	0.661	neutral	None	None	None	None	N
D/T	0.6918	likely_pathogenic	0.6109	pathogenic	-2.034	Highly Destabilizing	0.986	D	0.728	prob.delet.	None	None	None	None	N
D/V	0.7368	likely_pathogenic	0.658	pathogenic	-1.262	Destabilizing	0.991	D	0.774	deleterious	N	0.501106549	None	None	N
D/W	0.9758	likely_pathogenic	0.9697	pathogenic	-1.831	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
D/Y	0.5654	likely_pathogenic	0.5082	ambiguous	-1.591	Destabilizing	0.997	D	0.815	deleterious	N	0.471997151	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.