TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16457	49594;49595;49596	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
N2AB	14816	44671;44672;44673	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
N2A	13889	41890;41891;41892	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
N2B	7392	22399;22400;22401	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
Novex-1	7517	22774;22775;22776	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
Novex-2	7584	22975;22976;22977	chr2:178613914;178613913;178613912	chr2:179478641;179478640;179478639
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-7
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2087
• 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
L/P	None	None	0.999	N	0.876	0.503	0.730082620818	gnomAD-4.0.0	1.6036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.43546E-04	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
L/A	0.832	likely_pathogenic	0.8254	pathogenic	-2.304	Highly Destabilizing	0.966	D	0.728	prob.delet.	None	None	None	None	N
L/C	0.8717	likely_pathogenic	0.8525	pathogenic	-1.921	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/D	0.9985	likely_pathogenic	0.9987	pathogenic	-2.833	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/E	0.9899	likely_pathogenic	0.9912	pathogenic	-2.69	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
L/F	0.8992	likely_pathogenic	0.9046	pathogenic	-1.435	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
L/G	0.9845	likely_pathogenic	0.9844	pathogenic	-2.767	Highly Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
L/H	0.9893	likely_pathogenic	0.9901	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/I	0.1865	likely_benign	0.1884	benign	-1.006	Destabilizing	0.955	D	0.711	prob.delet.	N	0.497857021	None	None	N
L/K	0.9888	likely_pathogenic	0.9905	pathogenic	-1.723	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/M	0.4138	ambiguous	0.4262	ambiguous	-1.112	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
L/N	0.9864	likely_pathogenic	0.9883	pathogenic	-1.915	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
L/P	0.4752	ambiguous	0.4779	ambiguous	-1.416	Destabilizing	0.999	D	0.876	deleterious	N	0.448621083	None	None	N
L/Q	0.9727	likely_pathogenic	0.9749	pathogenic	-1.917	Destabilizing	0.999	D	0.875	deleterious	D	0.701596956	None	None	N
L/R	0.983	likely_pathogenic	0.9841	pathogenic	-1.363	Destabilizing	0.997	D	0.871	deleterious	D	0.701596956	None	None	N
L/S	0.9814	likely_pathogenic	0.9836	pathogenic	-2.53	Highly Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	N
L/T	0.8314	likely_pathogenic	0.8372	pathogenic	-2.258	Highly Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
L/V	0.1738	likely_benign	0.1641	benign	-1.416	Destabilizing	0.117	N	0.506	neutral	N	0.458660991	None	None	N
L/W	0.9846	likely_pathogenic	0.9881	pathogenic	-1.773	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/Y	0.9886	likely_pathogenic	0.9904	pathogenic	-1.498	Destabilizing	0.998	D	0.835	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.