TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16230	48913;48914;48915	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
N2AB	14589	43990;43991;43992	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
N2A	13662	41209;41210;41211	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
N2B	7165	21718;21719;21720	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
Novex-1	7290	22093;22094;22095	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
Novex-2	7357	22294;22295;22296	chr2:178614919;178614918;178614917	chr2:179479646;179479645;179479644
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: Fn3-5
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.1502
• 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/M	None	None	1.0	N	0.688	0.424	0.356281029322	gnomAD-4.0.0	1.64772E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9569E-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
K/A	0.8463	likely_pathogenic	0.7706	pathogenic	-1.009	Destabilizing	0.97	D	0.651	neutral	None	None	None	None	N
K/C	0.7855	likely_pathogenic	0.7441	pathogenic	-1.529	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/D	0.9897	likely_pathogenic	0.9836	pathogenic	-1.917	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	N
K/E	0.8093	likely_pathogenic	0.7286	pathogenic	-1.715	Destabilizing	0.961	D	0.689	prob.neutral	N	0.507635013	None	None	N
K/F	0.9514	likely_pathogenic	0.9343	pathogenic	-0.46	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/G	0.9586	likely_pathogenic	0.93	pathogenic	-1.411	Destabilizing	0.985	D	0.679	prob.neutral	None	None	None	None	N
K/H	0.7081	likely_pathogenic	0.6797	pathogenic	-1.777	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/I	0.6695	likely_pathogenic	0.595	pathogenic	0.082	Stabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
K/L	0.6788	likely_pathogenic	0.6114	pathogenic	0.082	Stabilizing	0.97	D	0.679	prob.neutral	None	None	None	None	N
K/M	0.4481	ambiguous	0.3644	ambiguous	-0.281	Destabilizing	1.0	D	0.688	prob.neutral	N	0.482814334	None	None	N
K/N	0.952	likely_pathogenic	0.9344	pathogenic	-1.755	Destabilizing	0.994	D	0.622	neutral	N	0.518941591	None	None	N
K/P	0.9988	likely_pathogenic	0.9977	pathogenic	-0.257	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
K/Q	0.4078	ambiguous	0.3508	ambiguous	-1.577	Destabilizing	0.989	D	0.641	neutral	N	0.464486478	None	None	N
K/R	0.1112	likely_benign	0.1044	benign	-1.412	Destabilizing	0.031	N	0.326	neutral	N	0.400127592	None	None	N
K/S	0.8917	likely_pathogenic	0.8361	pathogenic	-2.131	Highly Destabilizing	0.985	D	0.647	neutral	None	None	None	None	N
K/T	0.5858	likely_pathogenic	0.4609	ambiguous	-1.722	Destabilizing	0.98	D	0.639	neutral	N	0.467024883	None	None	N
K/V	0.6077	likely_pathogenic	0.5262	ambiguous	-0.257	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	N
K/W	0.9483	likely_pathogenic	0.9288	pathogenic	-0.631	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Y	0.8925	likely_pathogenic	0.875	pathogenic	-0.222	Destabilizing	0.999	D	0.757	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.