TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18605	56038;56039;56040	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
N2AB	16964	51115;51116;51117	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
N2A	16037	48334;48335;48336	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
N2B	9540	28843;28844;28845	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
Novex-1	9665	29218;29219;29220	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
Novex-2	9732	29419;29420;29421	chr2:178601091;178601090;178601089	chr2:179465818;179465817;179465816
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-23
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.5361
• Predicted PPI site: I

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
N/T	None	None	0.999	N	0.499	0.37	0.369682402691	gnomAD-4.0.0	1.61138E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.892E-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
N/A	0.7327	likely_pathogenic	0.7089	pathogenic	-0.473	Destabilizing	0.998	D	0.506	neutral	None	None	None	None	I
N/C	0.655	likely_pathogenic	0.6466	pathogenic	0.359	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
N/D	0.672	likely_pathogenic	0.6575	pathogenic	-0.238	Destabilizing	0.998	D	0.447	neutral	N	0.432473183	None	None	I
N/E	0.8793	likely_pathogenic	0.8811	pathogenic	-0.262	Destabilizing	0.997	D	0.467	neutral	None	None	None	None	I
N/F	0.742	likely_pathogenic	0.7108	pathogenic	-0.792	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
N/G	0.7638	likely_pathogenic	0.7466	pathogenic	-0.671	Destabilizing	0.998	D	0.406	neutral	None	None	None	None	I
N/H	0.2592	likely_benign	0.229	benign	-0.754	Destabilizing	0.64	D	0.245	neutral	N	0.496447304	None	None	I
N/I	0.6844	likely_pathogenic	0.6842	pathogenic	-0.032	Destabilizing	1.0	D	0.689	prob.neutral	N	0.515033065	None	None	I
N/K	0.8074	likely_pathogenic	0.7958	pathogenic	0.002	Stabilizing	0.998	D	0.502	neutral	N	0.479400339	None	None	I
N/L	0.6688	likely_pathogenic	0.6619	pathogenic	-0.032	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
N/M	0.6839	likely_pathogenic	0.6713	pathogenic	0.516	Stabilizing	1.0	D	0.606	neutral	None	None	None	None	I
N/P	0.9815	likely_pathogenic	0.9859	pathogenic	-0.152	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
N/Q	0.7565	likely_pathogenic	0.7482	pathogenic	-0.549	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	I
N/R	0.7598	likely_pathogenic	0.7436	pathogenic	0.084	Stabilizing	1.0	D	0.547	neutral	None	None	None	None	I
N/S	0.316	likely_benign	0.2871	benign	-0.258	Destabilizing	0.998	D	0.405	neutral	N	0.467663192	None	None	I
N/T	0.53	ambiguous	0.5227	ambiguous	-0.135	Destabilizing	0.999	D	0.499	neutral	N	0.497351381	None	None	I
N/V	0.687	likely_pathogenic	0.6808	pathogenic	-0.152	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
N/W	0.8685	likely_pathogenic	0.8538	pathogenic	-0.722	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
N/Y	0.2335	likely_benign	0.2312	benign	-0.473	Destabilizing	0.999	D	0.645	neutral	N	0.462777448	None	None	I

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.