TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22050	66373;66374;66375	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
N2AB	20409	61450;61451;61452	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
N2A	19482	58669;58670;58671	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
N2B	12985	39178;39179;39180	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
Novex-1	13110	39553;39554;39555	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
Novex-2	13177	39754;39755;39756	chr2:178582308;178582307;178582306	chr2:179447035;179447034;179447033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-47
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.4403
• 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
K/R	rs2047964470	None	0.988	N	0.562	0.214	0.347659731818	gnomAD-4.0.0	3.32615E-06	None	None	None	None	N	None	0	0	None	0	5.60036E-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
K/A	0.5357	ambiguous	0.4784	ambiguous	-0.289	Destabilizing	0.422	N	0.281	neutral	None	None	None	None	N
K/C	0.6603	likely_pathogenic	0.6134	pathogenic	-0.267	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/D	0.8803	likely_pathogenic	0.8586	pathogenic	-0.192	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
K/E	0.3238	likely_benign	0.2932	benign	-0.129	Destabilizing	0.988	D	0.481	neutral	N	0.49112406	None	None	N
K/F	0.8796	likely_pathogenic	0.8626	pathogenic	-0.155	Destabilizing	0.999	D	0.738	deleterious	None	None	None	None	N
K/G	0.7178	likely_pathogenic	0.6565	pathogenic	-0.615	Destabilizing	0.982	D	0.522	neutral	None	None	None	None	N
K/H	0.4086	ambiguous	0.3998	ambiguous	-1.086	Destabilizing	1.0	D	0.545	neutral	None	None	None	None	N
K/I	0.4669	ambiguous	0.4468	ambiguous	0.529	Stabilizing	0.997	D	0.753	deleterious	N	0.499899925	None	None	N
K/L	0.5592	ambiguous	0.5344	ambiguous	0.529	Stabilizing	0.982	D	0.495	neutral	None	None	None	None	N
K/M	0.3949	ambiguous	0.3576	ambiguous	0.492	Stabilizing	1.0	D	0.522	neutral	None	None	None	None	N
K/N	0.7381	likely_pathogenic	0.7136	pathogenic	-0.189	Destabilizing	0.999	D	0.542	neutral	N	0.509988783	None	None	N
K/P	0.9854	likely_pathogenic	0.981	pathogenic	0.287	Stabilizing	0.997	D	0.558	neutral	None	None	None	None	N
K/Q	0.1593	likely_benign	0.1515	benign	-0.344	Destabilizing	0.999	D	0.576	neutral	D	0.532403396	None	None	N
K/R	0.0787	likely_benign	0.0768	benign	-0.495	Destabilizing	0.988	D	0.562	neutral	N	0.484129447	None	None	N
K/S	0.6453	likely_pathogenic	0.6071	pathogenic	-0.74	Destabilizing	0.965	D	0.457	neutral	None	None	None	None	N
K/T	0.292	likely_benign	0.2707	benign	-0.495	Destabilizing	0.993	D	0.528	neutral	N	0.504158002	None	None	N
K/V	0.3339	likely_benign	0.3183	benign	0.287	Stabilizing	0.995	D	0.465	neutral	None	None	None	None	N
K/W	0.8756	likely_pathogenic	0.8615	pathogenic	-0.076	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/Y	0.8201	likely_pathogenic	0.7897	pathogenic	0.231	Stabilizing	0.999	D	0.684	prob.delet.	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.