TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28913	86962;86963;86964	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
N2AB	27272	82039;82040;82041	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
N2A	26345	79258;79259;79260	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
N2B	19848	59767;59768;59769	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
Novex-1	19973	60142;60143;60144	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
Novex-2	20040	60343;60344;60345	chr2:178559395;178559394;178559393	chr2:179424122;179424121;179424120
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: Fn3-98
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1208
• 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/P	rs2154157801	None	0.523	N	0.591	0.26	0.452834868696	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	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	0.3377	likely_benign	0.3762	ambiguous	-0.786	Destabilizing	0.983	D	0.533	neutral	None	None	None	None	N
A/D	0.437	ambiguous	0.4745	ambiguous	-1.666	Destabilizing	0.101	N	0.5	neutral	N	0.483195579	None	None	N
A/E	0.4474	ambiguous	0.4814	ambiguous	-1.589	Destabilizing	0.001	N	0.231	neutral	None	None	None	None	N
A/F	0.3761	ambiguous	0.402	ambiguous	-0.84	Destabilizing	0.94	D	0.603	neutral	None	None	None	None	N
A/G	0.1141	likely_benign	0.1204	benign	-1.35	Destabilizing	None	N	0.085	neutral	N	0.411719483	None	None	N
A/H	0.5434	ambiguous	0.5856	pathogenic	-1.659	Destabilizing	0.836	D	0.561	neutral	None	None	None	None	N
A/I	0.2802	likely_benign	0.2967	benign	-0.09	Destabilizing	0.836	D	0.603	neutral	None	None	None	None	N
A/K	0.6688	likely_pathogenic	0.7036	pathogenic	-1.249	Destabilizing	0.264	N	0.495	neutral	None	None	None	None	N
A/L	0.2248	likely_benign	0.2409	benign	-0.09	Destabilizing	0.418	N	0.524	neutral	None	None	None	None	N
A/M	0.2123	likely_benign	0.2296	benign	-0.061	Destabilizing	0.983	D	0.553	neutral	None	None	None	None	N
A/N	0.2425	likely_benign	0.2785	benign	-1.17	Destabilizing	0.418	N	0.535	neutral	None	None	None	None	N
A/P	0.8841	likely_pathogenic	0.8839	pathogenic	-0.345	Destabilizing	0.523	D	0.591	neutral	N	0.47347238	None	None	N
A/Q	0.419	ambiguous	0.4562	ambiguous	-1.181	Destabilizing	0.264	N	0.575	neutral	None	None	None	None	N
A/R	0.6123	likely_pathogenic	0.6471	pathogenic	-1.057	Destabilizing	0.418	N	0.581	neutral	None	None	None	None	N
A/S	0.0873	likely_benign	0.0919	benign	-1.553	Destabilizing	0.021	N	0.097	neutral	N	0.426243431	None	None	N
A/T	0.0915	likely_benign	0.0946	benign	-1.375	Destabilizing	0.213	N	0.4	neutral	N	0.400416693	None	None	N
A/V	0.1472	likely_benign	0.1554	benign	-0.345	Destabilizing	0.351	N	0.463	neutral	N	0.431419965	None	None	N
A/W	0.8145	likely_pathogenic	0.8353	pathogenic	-1.43	Destabilizing	0.983	D	0.577	neutral	None	None	None	None	N
A/Y	0.5204	ambiguous	0.5672	pathogenic	-0.921	Destabilizing	0.94	D	0.597	neutral	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.