TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24662	74209;74210;74211	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
N2AB	23021	69286;69287;69288	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
N2A	22094	66505;66506;66507	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
N2B	15597	47014;47015;47016	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
Novex-1	15722	47389;47390;47391	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
Novex-2	15789	47590;47591;47592	chr2:178572148;178572147;178572146	chr2:179436875;179436874;179436873
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: Fn3-67
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.4293
• 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/N	None	None	0.882	N	0.627	0.17	0.187945064343	gnomAD-4.0.0	1.59218E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85936E-06	0	0
K/R	None	None	0.003	N	0.353	0.146	0.241078983079	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.4586	ambiguous	0.4086	ambiguous	0.067	Stabilizing	0.739	D	0.563	neutral	None	None	None	None	N
K/C	0.747	likely_pathogenic	0.7133	pathogenic	-0.203	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.6845	likely_pathogenic	0.6206	pathogenic	-0.117	Destabilizing	0.909	D	0.616	neutral	None	None	None	None	N
K/E	0.2897	likely_benign	0.2526	benign	-0.122	Destabilizing	0.243	N	0.582	neutral	N	0.442903608	None	None	N
K/F	0.8623	likely_pathogenic	0.8101	pathogenic	-0.217	Destabilizing	0.968	D	0.687	prob.neutral	None	None	None	None	N
K/G	0.5944	likely_pathogenic	0.535	ambiguous	-0.09	Destabilizing	0.909	D	0.517	neutral	None	None	None	None	N
K/H	0.3102	likely_benign	0.2938	benign	-0.248	Destabilizing	0.969	D	0.639	neutral	None	None	None	None	N
K/I	0.4383	ambiguous	0.3837	ambiguous	0.398	Stabilizing	0.309	N	0.692	prob.neutral	N	0.520097742	None	None	N
K/L	0.4857	ambiguous	0.4345	ambiguous	0.398	Stabilizing	0.226	N	0.517	neutral	None	None	None	None	N
K/M	0.3436	ambiguous	0.3053	benign	0.066	Stabilizing	0.965	D	0.647	neutral	None	None	None	None	N
K/N	0.5072	ambiguous	0.4493	ambiguous	0.264	Stabilizing	0.882	D	0.627	neutral	N	0.508283238	None	None	N
K/P	0.9359	likely_pathogenic	0.9099	pathogenic	0.313	Stabilizing	0.953	D	0.599	neutral	None	None	None	None	N
K/Q	0.1554	likely_benign	0.1428	benign	0.109	Stabilizing	0.476	N	0.617	neutral	N	0.49419922	None	None	N
K/R	0.0788	likely_benign	0.0771	benign	0.036	Stabilizing	0.003	N	0.353	neutral	N	0.481982071	None	None	N
K/S	0.499	ambiguous	0.4462	ambiguous	-0.133	Destabilizing	0.739	D	0.572	neutral	None	None	None	None	N
K/T	0.2237	likely_benign	0.197	benign	-0.011	Destabilizing	0.693	D	0.583	neutral	N	0.463569668	None	None	N
K/V	0.405	ambiguous	0.3533	ambiguous	0.313	Stabilizing	0.278	N	0.622	neutral	None	None	None	None	N
K/W	0.8597	likely_pathogenic	0.8151	pathogenic	-0.301	Destabilizing	0.997	D	0.746	deleterious	None	None	None	None	N
K/Y	0.7199	likely_pathogenic	0.6629	pathogenic	0.054	Stabilizing	0.485	N	0.651	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.