TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20277	61054;61055;61056	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
N2AB	18636	56131;56132;56133	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
N2A	17709	53350;53351;53352	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
N2B	11212	33859;33860;33861	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
Novex-1	11337	34234;34235;34236	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
Novex-2	11404	34435;34436;34437	chr2:178590896;178590895;178590894	chr2:179455623;179455622;179455621
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: Fn3-35
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6685
• 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/T	rs2050069618	None	1.0	N	0.765	0.266	0.370240404367	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05

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	0.46	ambiguous	0.441	ambiguous	-0.307	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
K/C	0.7015	likely_pathogenic	0.6615	pathogenic	-0.341	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/D	0.753	likely_pathogenic	0.7505	pathogenic	0.113	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/E	0.2751	likely_benign	0.2795	benign	0.143	Stabilizing	0.999	D	0.677	prob.neutral	N	0.516844006	None	None	N
K/F	0.77	likely_pathogenic	0.7577	pathogenic	-0.43	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/G	0.7123	likely_pathogenic	0.7201	pathogenic	-0.565	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/H	0.4432	ambiguous	0.4279	ambiguous	-1.0	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/I	0.2826	likely_benign	0.2753	benign	0.312	Stabilizing	1.0	D	0.759	deleterious	N	0.515651927	None	None	N
K/L	0.3536	ambiguous	0.3419	ambiguous	0.312	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
K/M	0.209	likely_benign	0.2006	benign	0.342	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/N	0.5015	ambiguous	0.5151	ambiguous	0.063	Stabilizing	1.0	D	0.782	deleterious	N	0.48955583	None	None	N
K/P	0.4995	ambiguous	0.4627	ambiguous	0.135	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Q	0.1764	likely_benign	0.1684	benign	-0.176	Destabilizing	1.0	D	0.769	deleterious	N	0.468628772	None	None	N
K/R	0.1022	likely_benign	0.1024	benign	-0.214	Destabilizing	0.999	D	0.641	neutral	N	0.487926608	None	None	N
K/S	0.5248	ambiguous	0.5259	ambiguous	-0.578	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
K/T	0.2168	likely_benign	0.2128	benign	-0.376	Destabilizing	1.0	D	0.765	deleterious	N	0.451275162	None	None	N
K/V	0.2994	likely_benign	0.283	benign	0.135	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/W	0.8499	likely_pathogenic	0.8329	pathogenic	-0.317	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/Y	0.644	likely_pathogenic	0.6317	pathogenic	0.025	Stabilizing	1.0	D	0.75	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.