TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20373	61342;61343;61344	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
N2AB	18732	56419;56420;56421	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
N2A	17805	53638;53639;53640	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
N2B	11308	34147;34148;34149	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
Novex-1	11433	34522;34523;34524	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
Novex-2	11500	34723;34724;34725	chr2:178590608;178590607;178590606	chr2:179455335;179455334;179455333
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-36
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2764
• 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
G/R	None	None	0.803	N	0.475	0.355	0.234412748748	gnomAD-4.0.0	1.36919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79959E-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
G/A	0.4235	ambiguous	0.3781	ambiguous	-0.746	Destabilizing	0.992	D	0.556	neutral	N	0.484418659	None	None	N
G/C	0.7279	likely_pathogenic	0.677	pathogenic	-1.041	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
G/D	0.9028	likely_pathogenic	0.7767	pathogenic	-1.469	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
G/E	0.9127	likely_pathogenic	0.8263	pathogenic	-1.572	Destabilizing	0.999	D	0.743	deleterious	N	0.471883812	None	None	N
G/F	0.9322	likely_pathogenic	0.9109	pathogenic	-1.282	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/H	0.9487	likely_pathogenic	0.914	pathogenic	-1.274	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/I	0.9086	likely_pathogenic	0.8812	pathogenic	-0.548	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/K	0.9687	likely_pathogenic	0.9407	pathogenic	-1.25	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
G/L	0.867	likely_pathogenic	0.8275	pathogenic	-0.548	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/M	0.9158	likely_pathogenic	0.8932	pathogenic	-0.432	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
G/N	0.885	likely_pathogenic	0.8133	pathogenic	-0.912	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
G/P	0.9883	likely_pathogenic	0.9858	pathogenic	-0.577	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/Q	0.919	likely_pathogenic	0.8734	pathogenic	-1.196	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
G/R	0.9405	likely_pathogenic	0.9046	pathogenic	-0.862	Destabilizing	0.803	D	0.475	neutral	N	0.485432617	None	None	N
G/S	0.2996	likely_benign	0.2543	benign	-1.074	Destabilizing	0.967	D	0.396	neutral	None	None	None	None	N
G/T	0.6962	likely_pathogenic	0.6268	pathogenic	-1.116	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	N
G/V	0.845	likely_pathogenic	0.8035	pathogenic	-0.577	Destabilizing	0.999	D	0.794	deleterious	N	0.482318745	None	None	N
G/W	0.9284	likely_pathogenic	0.9013	pathogenic	-1.541	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
G/Y	0.9226	likely_pathogenic	0.8833	pathogenic	-1.167	Destabilizing	1.0	D	0.818	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.