TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20371	61336;61337;61338	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
N2AB	18730	56413;56414;56415	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
N2A	17803	53632;53633;53634	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
N2B	11306	34141;34142;34143	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
Novex-1	11431	34516;34517;34518	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
Novex-2	11498	34717;34718;34719	chr2:178590614;178590613;178590612	chr2:179455341;179455340;179455339
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-36
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4843
• Predicted PPI site: I

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
P/T	rs1227565945	-0.168	0.953	N	0.601	0.263	0.232513804876	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
P/T	rs1227565945	-0.168	0.953	N	0.601	0.263	0.232513804876	gnomAD-4.0.0	1.59326E-06	None	None	None	None	I	None	0	0	None	0	2.77824E-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
P/A	0.1152	likely_benign	0.1097	benign	-0.401	Destabilizing	0.893	D	0.491	neutral	N	0.448940483	None	None	I
P/C	0.629	likely_pathogenic	0.5871	pathogenic	-0.634	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/D	0.8844	likely_pathogenic	0.8376	pathogenic	0.046	Stabilizing	0.998	D	0.538	neutral	None	None	None	None	I
P/E	0.6108	likely_pathogenic	0.5044	ambiguous	-0.071	Destabilizing	0.998	D	0.505	neutral	None	None	None	None	I
P/F	0.7889	likely_pathogenic	0.7257	pathogenic	-0.722	Destabilizing	0.995	D	0.803	deleterious	None	None	None	None	I
P/G	0.6961	likely_pathogenic	0.6613	pathogenic	-0.511	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	I
P/H	0.5165	ambiguous	0.432	ambiguous	-0.146	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/I	0.325	likely_benign	0.2446	benign	-0.27	Destabilizing	0.931	D	0.614	neutral	None	None	None	None	I
P/K	0.4458	ambiguous	0.3552	ambiguous	-0.173	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	I
P/L	0.1703	likely_benign	0.14	benign	-0.27	Destabilizing	0.91	D	0.609	neutral	N	0.502247408	None	None	I
P/M	0.3889	ambiguous	0.3305	benign	-0.263	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	I
P/N	0.731	likely_pathogenic	0.6454	pathogenic	0.041	Stabilizing	0.998	D	0.802	deleterious	None	None	None	None	I
P/Q	0.3248	likely_benign	0.2548	benign	-0.204	Destabilizing	0.998	D	0.501	neutral	N	0.473453974	None	None	I
P/R	0.3628	ambiguous	0.2899	benign	0.266	Stabilizing	0.998	D	0.823	deleterious	N	0.459108701	None	None	I
P/S	0.3573	ambiguous	0.305	benign	-0.366	Destabilizing	0.993	D	0.503	neutral	N	0.466617119	None	None	I
P/T	0.2101	likely_benign	0.1646	benign	-0.379	Destabilizing	0.953	D	0.601	neutral	N	0.491686484	None	None	I
P/V	0.2066	likely_benign	0.164	benign	-0.28	Destabilizing	0.132	N	0.442	neutral	None	None	None	None	I
P/W	0.9105	likely_pathogenic	0.8848	pathogenic	-0.775	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/Y	0.7518	likely_pathogenic	0.6882	pathogenic	-0.447	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I

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.