TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24911	74956;74957;74958	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
N2AB	23270	70033;70034;70035	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
N2A	22343	67252;67253;67254	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
N2B	15846	47761;47762;47763	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
Novex-1	15971	48136;48137;48138	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
Novex-2	16038	48337;48338;48339	chr2:178571401;178571400;178571399	chr2:179436128;179436127;179436126
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-69
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3727
• 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
P/L	rs750688079	-0.658	0.999	N	0.755	0.439	0.74914240937	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/L	rs750688079	-0.658	0.999	N	0.755	0.439	0.74914240937	gnomAD-4.0.0	2.05305E-06	None	None	None	None	I	None	2.98989E-05	4.47287E-05	None	0	0	None	0	0	0	0	0
P/S	None	None	0.905	N	0.423	0.199	0.374434639691	gnomAD-4.0.0	1.59204E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85948E-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
P/A	0.0997	likely_benign	0.0929	benign	-1.316	Destabilizing	0.992	D	0.687	prob.neutral	N	0.464777603	None	None	I
P/C	0.5491	ambiguous	0.4904	ambiguous	-1.098	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
P/D	0.8991	likely_pathogenic	0.8678	pathogenic	-1.132	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
P/E	0.6025	likely_pathogenic	0.5445	ambiguous	-1.17	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
P/F	0.6733	likely_pathogenic	0.6062	pathogenic	-1.223	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/G	0.6433	likely_pathogenic	0.5897	pathogenic	-1.569	Destabilizing	0.997	D	0.725	prob.delet.	None	None	None	None	I
P/H	0.4815	ambiguous	0.4222	ambiguous	-1.057	Destabilizing	1.0	D	0.827	deleterious	D	0.532953386	None	None	I
P/I	0.3868	ambiguous	0.3313	benign	-0.741	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/K	0.6725	likely_pathogenic	0.6191	pathogenic	-0.889	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
P/L	0.2444	likely_benign	0.2097	benign	-0.741	Destabilizing	0.999	D	0.755	deleterious	N	0.514595641	None	None	I
P/M	0.4132	ambiguous	0.3558	ambiguous	-0.649	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
P/N	0.6907	likely_pathogenic	0.6314	pathogenic	-0.688	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
P/Q	0.3287	likely_benign	0.297	benign	-0.95	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/R	0.5357	ambiguous	0.4889	ambiguous	-0.393	Destabilizing	0.999	D	0.819	deleterious	N	0.508555254	None	None	I
P/S	0.243	likely_benign	0.2121	benign	-1.207	Destabilizing	0.905	D	0.423	neutral	N	0.519540381	None	None	I
P/T	0.2486	likely_benign	0.2184	benign	-1.142	Destabilizing	0.992	D	0.707	prob.neutral	N	0.482817676	None	None	I
P/V	0.2905	likely_benign	0.2521	benign	-0.899	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
P/W	0.8848	likely_pathogenic	0.851	pathogenic	-1.301	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
P/Y	0.7064	likely_pathogenic	0.6473	pathogenic	-0.995	Destabilizing	1.0	D	0.854	deleterious	None	None	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.