TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22152	66679;66680;66681	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
N2AB	20511	61756;61757;61758	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
N2A	19584	58975;58976;58977	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
N2B	13087	39484;39485;39486	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
Novex-1	13212	39859;39860;39861	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
Novex-2	13279	40060;40061;40062	chr2:178581915;178581914;178581913	chr2:179446642;179446641;179446640
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-48
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.0461
• 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
D/E	None	None	0.999	N	0.505	0.189	0.254244900254	gnomAD-4.0.0	1.59298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-05	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
D/A	0.8943	likely_pathogenic	0.9229	pathogenic	-0.136	Destabilizing	1.0	D	0.783	deleterious	N	0.51301148	None	None	N
D/C	0.9814	likely_pathogenic	0.9899	pathogenic	-0.025	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/E	0.7199	likely_pathogenic	0.7693	pathogenic	-0.218	Destabilizing	0.999	D	0.505	neutral	N	0.465142962	None	None	N
D/F	0.9754	likely_pathogenic	0.9808	pathogenic	-0.158	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
D/G	0.945	likely_pathogenic	0.9607	pathogenic	-0.298	Destabilizing	1.0	D	0.826	deleterious	N	0.517302579	None	None	N
D/H	0.9331	likely_pathogenic	0.9578	pathogenic	0.151	Stabilizing	1.0	D	0.898	deleterious	N	0.461348243	None	None	N
D/I	0.9421	likely_pathogenic	0.9613	pathogenic	0.233	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/K	0.9689	likely_pathogenic	0.9778	pathogenic	0.317	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
D/L	0.9248	likely_pathogenic	0.944	pathogenic	0.233	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/M	0.9834	likely_pathogenic	0.9877	pathogenic	0.207	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/N	0.636	likely_pathogenic	0.6969	pathogenic	0.126	Stabilizing	1.0	D	0.824	deleterious	N	0.513704913	None	None	N
D/P	0.971	likely_pathogenic	0.9758	pathogenic	0.131	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
D/Q	0.958	likely_pathogenic	0.971	pathogenic	0.14	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/R	0.9761	likely_pathogenic	0.9831	pathogenic	0.51	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/S	0.8054	likely_pathogenic	0.8515	pathogenic	0.002	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/T	0.9456	likely_pathogenic	0.9592	pathogenic	0.124	Stabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
D/V	0.894	likely_pathogenic	0.9271	pathogenic	0.131	Stabilizing	1.0	D	0.827	deleterious	N	0.473905863	None	None	N
D/W	0.9951	likely_pathogenic	0.9957	pathogenic	-0.078	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
D/Y	0.8403	likely_pathogenic	0.8821	pathogenic	0.066	Stabilizing	1.0	D	0.835	deleterious	N	0.488998378	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.