TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22119	66580;66581;66582	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
N2AB	20478	61657;61658;61659	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
N2A	19551	58876;58877;58878	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
N2B	13054	39385;39386;39387	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
Novex-1	13179	39760;39761;39762	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
Novex-2	13246	39961;39962;39963	chr2:178582014;178582013;178582012	chr2:179446741;179446740;179446739
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-48
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.5504
• 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
G/S	rs901951990	-0.28	0.698	N	0.381	0.208	0.214338557667	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	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
G/A	0.2151	likely_benign	0.258	benign	-0.315	Destabilizing	0.822	D	0.395	neutral	N	0.494401018	None	None	N
G/C	0.3414	ambiguous	0.3604	ambiguous	-0.821	Destabilizing	0.997	D	0.639	neutral	N	0.518545661	None	None	N
G/D	0.4839	ambiguous	0.5307	ambiguous	-0.531	Destabilizing	0.698	D	0.413	neutral	N	0.47626682	None	None	N
G/E	0.5815	likely_pathogenic	0.6506	pathogenic	-0.664	Destabilizing	0.076	N	0.322	neutral	None	None	None	None	N
G/F	0.7833	likely_pathogenic	0.8272	pathogenic	-0.94	Destabilizing	0.993	D	0.595	neutral	None	None	None	None	N
G/H	0.6044	likely_pathogenic	0.6336	pathogenic	-0.65	Destabilizing	0.978	D	0.531	neutral	None	None	None	None	N
G/I	0.6072	likely_pathogenic	0.6997	pathogenic	-0.311	Destabilizing	0.978	D	0.589	neutral	None	None	None	None	N
G/K	0.8177	likely_pathogenic	0.8384	pathogenic	-0.861	Destabilizing	0.754	D	0.448	neutral	None	None	None	None	N
G/L	0.6369	likely_pathogenic	0.7113	pathogenic	-0.311	Destabilizing	0.956	D	0.557	neutral	None	None	None	None	N
G/M	0.634	likely_pathogenic	0.7059	pathogenic	-0.443	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
G/N	0.3006	likely_benign	0.3643	ambiguous	-0.468	Destabilizing	0.043	N	0.257	neutral	None	None	None	None	N
G/P	0.9386	likely_pathogenic	0.9583	pathogenic	-0.276	Destabilizing	0.993	D	0.509	neutral	None	None	None	None	N
G/Q	0.5741	likely_pathogenic	0.6249	pathogenic	-0.703	Destabilizing	0.193	N	0.301	neutral	None	None	None	None	N
G/R	0.7121	likely_pathogenic	0.7182	pathogenic	-0.468	Destabilizing	0.942	D	0.499	neutral	N	0.470029339	None	None	N
G/S	0.1303	likely_benign	0.1553	benign	-0.644	Destabilizing	0.698	D	0.381	neutral	N	0.469268871	None	None	N
G/T	0.2859	likely_benign	0.354	ambiguous	-0.696	Destabilizing	0.86	D	0.473	neutral	None	None	None	None	N
G/V	0.4643	ambiguous	0.5518	ambiguous	-0.276	Destabilizing	0.97	D	0.561	neutral	N	0.518292171	None	None	N
G/W	0.7226	likely_pathogenic	0.724	pathogenic	-1.148	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
G/Y	0.6684	likely_pathogenic	0.7085	pathogenic	-0.769	Destabilizing	0.993	D	0.595	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.