TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31603	95032;95033;95034	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
N2AB	29962	90109;90110;90111	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
N2A	29035	87328;87329;87330	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
N2B	22538	67837;67838;67839	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
Novex-1	22663	68212;68213;68214	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
Novex-2	22730	68413;68414;68415	chr2:178546621;178546620;178546619	chr2:179411348;179411347;179411346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-118
• Domain position: 98
• Structural Position: 127
• Q(SASA): 0.1518
• 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
V/F	rs1060500567	None	0.449	N	0.752	0.236	0.568892413138	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs1060500567	None	0.449	N	0.752	0.236	0.568892413138	gnomAD-4.0.0	1.24184E-06	None	None	None	None	N	None	1.33579E-05	0	None	0	0	None	0	0	8.49475E-07	0	0
V/I	None	None	0.001	N	0.196	0.029	0.139678290688	gnomAD-4.0.0	6.85721E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16055E-05	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
V/A	0.6925	likely_pathogenic	0.672	pathogenic	-1.734	Destabilizing	0.189	N	0.602	neutral	N	0.481457642	None	None	N
V/C	0.9097	likely_pathogenic	0.8966	pathogenic	-1.29	Destabilizing	0.962	D	0.741	deleterious	None	None	None	None	N
V/D	0.9809	likely_pathogenic	0.9762	pathogenic	-1.853	Destabilizing	0.623	D	0.814	deleterious	N	0.515414881	None	None	N
V/E	0.9028	likely_pathogenic	0.8881	pathogenic	-1.684	Destabilizing	0.687	D	0.784	deleterious	None	None	None	None	N
V/F	0.5114	ambiguous	0.4914	ambiguous	-1.064	Destabilizing	0.449	N	0.752	deleterious	N	0.514654412	None	None	N
V/G	0.87	likely_pathogenic	0.8542	pathogenic	-2.23	Highly Destabilizing	0.623	D	0.813	deleterious	N	0.515161391	None	None	N
V/H	0.9622	likely_pathogenic	0.9525	pathogenic	-1.88	Destabilizing	0.962	D	0.834	deleterious	None	None	None	None	N
V/I	0.072	likely_benign	0.0706	benign	-0.392	Destabilizing	0.001	N	0.196	neutral	N	0.43293733	None	None	N
V/K	0.911	likely_pathogenic	0.8862	pathogenic	-1.496	Destabilizing	0.687	D	0.792	deleterious	None	None	None	None	N
V/L	0.3641	ambiguous	0.3351	benign	-0.392	Destabilizing	0.016	N	0.453	neutral	N	0.465515753	None	None	N
V/M	0.3287	likely_benign	0.3048	benign	-0.372	Destabilizing	0.519	D	0.649	prob.neutral	None	None	None	None	N
V/N	0.9347	likely_pathogenic	0.9157	pathogenic	-1.676	Destabilizing	0.87	D	0.833	deleterious	None	None	None	None	N
V/P	0.9903	likely_pathogenic	0.9873	pathogenic	-0.808	Destabilizing	0.87	D	0.783	deleterious	None	None	None	None	N
V/Q	0.872	likely_pathogenic	0.8495	pathogenic	-1.572	Destabilizing	0.87	D	0.81	deleterious	None	None	None	None	N
V/R	0.8733	likely_pathogenic	0.8441	pathogenic	-1.277	Destabilizing	0.687	D	0.843	deleterious	None	None	None	None	N
V/S	0.8676	likely_pathogenic	0.8475	pathogenic	-2.316	Highly Destabilizing	0.687	D	0.765	deleterious	None	None	None	None	N
V/T	0.6928	likely_pathogenic	0.6399	pathogenic	-1.995	Destabilizing	0.236	N	0.647	neutral	None	None	None	None	N
V/W	0.9783	likely_pathogenic	0.9735	pathogenic	-1.482	Destabilizing	0.962	D	0.789	deleterious	None	None	None	None	N
V/Y	0.9035	likely_pathogenic	0.8883	pathogenic	-1.08	Destabilizing	0.687	D	0.739	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.