TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22983	69172;69173;69174	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
N2AB	21342	64249;64250;64251	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
N2A	20415	61468;61469;61470	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
N2B	13918	41977;41978;41979	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
Novex-1	14043	42352;42353;42354	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
Novex-2	14110	42553;42554;42555	chr2:178577388;178577387;178577386	chr2:179442115;179442114;179442113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-128
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.2108
• 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
K/N	rs2046672689	None	0.638	N	0.601	0.246	0.18274738541	gnomAD-4.0.0	6.84466E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-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
K/A	0.7964	likely_pathogenic	0.7481	pathogenic	-1.031	Destabilizing	0.399	N	0.52	neutral	None	None	None	None	N
K/C	0.7652	likely_pathogenic	0.7054	pathogenic	-1.016	Destabilizing	0.982	D	0.807	deleterious	None	None	None	None	N
K/D	0.9518	likely_pathogenic	0.9432	pathogenic	0.165	Stabilizing	0.7	D	0.699	prob.neutral	None	None	None	None	N
K/E	0.6485	likely_pathogenic	0.6109	pathogenic	0.278	Stabilizing	0.201	N	0.457	neutral	N	0.517600019	None	None	N
K/F	0.8153	likely_pathogenic	0.7752	pathogenic	-1.049	Destabilizing	0.947	D	0.789	deleterious	None	None	None	None	N
K/G	0.8816	likely_pathogenic	0.8558	pathogenic	-1.346	Destabilizing	0.7	D	0.686	prob.neutral	None	None	None	None	N
K/H	0.426	ambiguous	0.3756	ambiguous	-1.742	Destabilizing	0.947	D	0.744	deleterious	None	None	None	None	N
K/I	0.5402	ambiguous	0.4647	ambiguous	-0.217	Destabilizing	0.826	D	0.785	deleterious	None	None	None	None	N
K/L	0.5585	ambiguous	0.4983	ambiguous	-0.217	Destabilizing	0.7	D	0.686	prob.neutral	None	None	None	None	N
K/M	0.4344	ambiguous	0.3945	ambiguous	-0.183	Destabilizing	0.976	D	0.733	prob.delet.	N	0.51734653	None	None	N
K/N	0.8505	likely_pathogenic	0.8359	pathogenic	-0.412	Destabilizing	0.638	D	0.601	neutral	N	0.51059858	None	None	N
K/P	0.9864	likely_pathogenic	0.9807	pathogenic	-0.462	Destabilizing	0.826	D	0.721	prob.delet.	None	None	None	None	N
K/Q	0.3078	likely_benign	0.2812	benign	-0.536	Destabilizing	0.468	N	0.59	neutral	N	0.496101949	None	None	N
K/R	0.0757	likely_benign	0.0714	benign	-0.468	Destabilizing	0.002	N	0.263	neutral	N	0.502754414	None	None	N
K/S	0.8491	likely_pathogenic	0.8273	pathogenic	-1.271	Destabilizing	0.399	N	0.525	neutral	None	None	None	None	N
K/T	0.6337	likely_pathogenic	0.5854	pathogenic	-0.945	Destabilizing	0.638	D	0.675	prob.neutral	N	0.494051261	None	None	N
K/V	0.5307	ambiguous	0.4563	ambiguous	-0.462	Destabilizing	0.7	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.8171	likely_pathogenic	0.7732	pathogenic	-0.828	Destabilizing	0.982	D	0.788	deleterious	None	None	None	None	N
K/Y	0.6926	likely_pathogenic	0.6443	pathogenic	-0.505	Destabilizing	0.826	D	0.769	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.