TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14634	44125;44126;44127	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
N2AB	12993	39202;39203;39204	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
N2A	12066	36421;36422;36423	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
N2B	5569	16930;16931;16932	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
Novex-1	5694	17305;17306;17307	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
Novex-2	5761	17506;17507;17508	chr2:178631148;178631147;178631146	chr2:179495875;179495874;179495873
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-97
• Domain position: 49
• Structural Position: 125
• Q(SASA): 0.5496
• 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	rs763794623	0.143	0.997	D	0.479	0.302	0.297718772494	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs763794623	0.143	0.997	D	0.479	0.302	0.297718772494	gnomAD-4.0.0	2.05321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69881E-06	0	0
K/Q	None	None	0.659	N	0.268	0.177	0.231231049324	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85956E-06	0	0
K/R	None	None	0.98	N	0.473	0.169	0.419835214384	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	0.4495	ambiguous	0.4521	ambiguous	-0.132	Destabilizing	0.985	D	0.505	neutral	None	None	None	None	N
K/C	0.8544	likely_pathogenic	0.8462	pathogenic	-0.277	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/D	0.7588	likely_pathogenic	0.7926	pathogenic	0.073	Stabilizing	0.996	D	0.527	neutral	None	None	None	None	N
K/E	0.1933	likely_benign	0.2097	benign	0.137	Stabilizing	0.961	D	0.525	neutral	N	0.508647459	None	None	N
K/F	0.8213	likely_pathogenic	0.8254	pathogenic	-0.047	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
K/G	0.6853	likely_pathogenic	0.7047	pathogenic	-0.419	Destabilizing	0.993	D	0.546	neutral	None	None	None	None	N
K/H	0.4248	ambiguous	0.4226	ambiguous	-0.684	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
K/I	0.3361	likely_benign	0.325	benign	0.574	Stabilizing	0.671	D	0.389	neutral	None	None	None	None	N
K/L	0.4105	ambiguous	0.407	ambiguous	0.574	Stabilizing	0.971	D	0.541	neutral	None	None	None	None	N
K/M	0.2501	likely_benign	0.2442	benign	0.23	Stabilizing	0.997	D	0.596	neutral	D	0.573070558	None	None	N
K/N	0.5559	ambiguous	0.5893	pathogenic	0.003	Stabilizing	0.997	D	0.479	neutral	D	0.546880022	None	None	N
K/P	0.9408	likely_pathogenic	0.9607	pathogenic	0.369	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/Q	0.1612	likely_benign	0.1527	benign	-0.069	Destabilizing	0.659	D	0.268	neutral	N	0.510902964	None	None	N
K/R	0.1081	likely_benign	0.1046	benign	-0.246	Destabilizing	0.98	D	0.473	neutral	N	0.511072729	None	None	N
K/S	0.5234	ambiguous	0.5382	ambiguous	-0.516	Destabilizing	0.985	D	0.457	neutral	None	None	None	None	N
K/T	0.1785	likely_benign	0.1791	benign	-0.272	Destabilizing	0.99	D	0.511	neutral	N	0.509221487	None	None	N
K/V	0.3498	ambiguous	0.3312	benign	0.369	Stabilizing	0.971	D	0.538	neutral	None	None	None	None	N
K/W	0.8695	likely_pathogenic	0.8742	pathogenic	-0.033	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/Y	0.7151	likely_pathogenic	0.7357	pathogenic	0.286	Stabilizing	0.999	D	0.661	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.