TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24296	73111;73112;73113	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
N2AB	22655	68188;68189;68190	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
N2A	21728	65407;65408;65409	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
N2B	15231	45916;45917;45918	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
Novex-1	15356	46291;46292;46293	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
Novex-2	15423	46492;46493;46494	chr2:178573246;178573245;178573244	chr2:179437973;179437972;179437971
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-64
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1641
• 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
R/G	None	None	0.994	D	0.631	0.526	0.65411270277	gnomAD-4.0.0	6.87461E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66539E-05

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
R/A	0.9375	likely_pathogenic	0.8928	pathogenic	-1.828	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
R/C	0.3432	ambiguous	0.2569	benign	-1.74	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/D	0.9924	likely_pathogenic	0.9876	pathogenic	-0.891	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
R/E	0.9024	likely_pathogenic	0.8456	pathogenic	-0.675	Destabilizing	0.992	D	0.592	neutral	None	None	None	None	N
R/F	0.9539	likely_pathogenic	0.9244	pathogenic	-1.01	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
R/G	0.9321	likely_pathogenic	0.8785	pathogenic	-2.177	Highly Destabilizing	0.994	D	0.631	neutral	D	0.565011294	None	None	N
R/H	0.173	likely_benign	0.1729	benign	-1.994	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
R/I	0.863	likely_pathogenic	0.8023	pathogenic	-0.817	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
R/K	0.3427	ambiguous	0.2809	benign	-1.202	Destabilizing	0.543	D	0.311	neutral	N	0.511201827	None	None	N
R/L	0.7849	likely_pathogenic	0.7191	pathogenic	-0.817	Destabilizing	0.996	D	0.631	neutral	None	None	None	None	N
R/M	0.8634	likely_pathogenic	0.7797	pathogenic	-1.337	Destabilizing	1.0	D	0.645	neutral	D	0.538766737	None	None	N
R/N	0.9535	likely_pathogenic	0.9351	pathogenic	-1.203	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	N
R/P	0.998	likely_pathogenic	0.9972	pathogenic	-1.142	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/Q	0.216	likely_benign	0.1704	benign	-1.055	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
R/S	0.9416	likely_pathogenic	0.903	pathogenic	-2.069	Highly Destabilizing	0.989	D	0.6	neutral	D	0.52550742	None	None	N
R/T	0.9057	likely_pathogenic	0.8411	pathogenic	-1.643	Destabilizing	0.998	D	0.6	neutral	N	0.507011544	None	None	N
R/V	0.8829	likely_pathogenic	0.8242	pathogenic	-1.142	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
R/W	0.6192	likely_pathogenic	0.5347	ambiguous	-0.558	Destabilizing	1.0	D	0.666	neutral	D	0.565264783	None	None	N
R/Y	0.8536	likely_pathogenic	0.7906	pathogenic	-0.401	Destabilizing	1.0	D	0.709	prob.delet.	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.