TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22161	66706;66707;66708	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
N2AB	20520	61783;61784;61785	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
N2A	19593	59002;59003;59004	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
N2B	13096	39511;39512;39513	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
Novex-1	13221	39886;39887;39888	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
Novex-2	13288	40087;40088;40089	chr2:178581787;178581786;178581785	chr2:179446514;179446513;179446512
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-49
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2451
• 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
A/T	rs886038883	None	0.056	N	0.273	0.184	0.115124310173	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	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
A/C	0.5167	ambiguous	0.5258	ambiguous	-0.678	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
A/D	0.8515	likely_pathogenic	0.876	pathogenic	-0.943	Destabilizing	0.967	D	0.781	deleterious	N	0.428995735	None	None	N
A/E	0.8095	likely_pathogenic	0.8364	pathogenic	-0.98	Destabilizing	0.975	D	0.686	prob.neutral	None	None	None	None	N
A/F	0.6774	likely_pathogenic	0.6715	pathogenic	-0.832	Destabilizing	0.987	D	0.808	deleterious	None	None	None	None	N
A/G	0.2729	likely_benign	0.2627	benign	-0.942	Destabilizing	0.025	N	0.261	neutral	N	0.372216945	None	None	N
A/H	0.8086	likely_pathogenic	0.8223	pathogenic	-1.163	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
A/I	0.4965	ambiguous	0.4643	ambiguous	-0.213	Destabilizing	0.975	D	0.752	deleterious	None	None	None	None	N
A/K	0.9099	likely_pathogenic	0.9203	pathogenic	-1.099	Destabilizing	0.975	D	0.713	prob.delet.	None	None	None	None	N
A/L	0.3977	ambiguous	0.3819	ambiguous	-0.213	Destabilizing	0.845	D	0.641	neutral	None	None	None	None	N
A/M	0.5223	ambiguous	0.486	ambiguous	-0.203	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
A/N	0.5763	likely_pathogenic	0.5494	ambiguous	-0.778	Destabilizing	0.975	D	0.797	deleterious	None	None	None	None	N
A/P	0.6702	likely_pathogenic	0.7026	pathogenic	-0.335	Destabilizing	0.983	D	0.754	deleterious	N	0.474613381	None	None	N
A/Q	0.6713	likely_pathogenic	0.6836	pathogenic	-0.921	Destabilizing	0.987	D	0.769	deleterious	None	None	None	None	N
A/R	0.8043	likely_pathogenic	0.8436	pathogenic	-0.764	Destabilizing	0.975	D	0.756	deleterious	None	None	None	None	N
A/S	0.1349	likely_benign	0.1256	benign	-1.084	Destabilizing	0.805	D	0.485	neutral	N	0.39549645	None	None	N
A/T	0.2081	likely_benign	0.1901	benign	-1.028	Destabilizing	0.056	N	0.273	neutral	N	0.405462727	None	None	N
A/V	0.2785	likely_benign	0.2675	benign	-0.335	Destabilizing	0.805	D	0.533	neutral	N	0.411218051	None	None	N
A/W	0.931	likely_pathogenic	0.9437	pathogenic	-1.198	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
A/Y	0.7629	likely_pathogenic	0.7703	pathogenic	-0.783	Destabilizing	0.996	D	0.803	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.