TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24022	72289;72290;72291	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
N2AB	22381	67366;67367;67368	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
N2A	21454	64585;64586;64587	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
N2B	14957	45094;45095;45096	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
Novex-1	15082	45469;45470;45471	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
Novex-2	15149	45670;45671;45672	chr2:178574068;178574067;178574066	chr2:179438795;179438794;179438793
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-62
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.2777
• 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/N	rs767886519	-0.226	1.0	N	0.72	0.338	0.276482976112	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.6154E-04	None	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
D/A	0.7288	likely_pathogenic	0.8537	pathogenic	-0.233	Destabilizing	1.0	D	0.679	prob.neutral	N	0.49470536	None	None	N
D/C	0.9782	likely_pathogenic	0.9881	pathogenic	0.078	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/E	0.6801	likely_pathogenic	0.8119	pathogenic	-0.242	Destabilizing	0.999	D	0.48	neutral	N	0.488683465	None	None	N
D/F	0.9621	likely_pathogenic	0.98	pathogenic	-0.284	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
D/G	0.7135	likely_pathogenic	0.8262	pathogenic	-0.405	Destabilizing	1.0	D	0.733	deleterious	N	0.48146569	None	None	N
D/H	0.9008	likely_pathogenic	0.9445	pathogenic	-0.122	Destabilizing	1.0	D	0.843	deleterious	N	0.484000586	None	None	N
D/I	0.9336	likely_pathogenic	0.9675	pathogenic	0.166	Stabilizing	1.0	D	0.73	deleterious	None	None	None	None	N
D/K	0.9393	likely_pathogenic	0.9687	pathogenic	0.32	Stabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
D/L	0.8957	likely_pathogenic	0.9496	pathogenic	0.166	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
D/M	0.9644	likely_pathogenic	0.9829	pathogenic	0.291	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/N	0.4455	ambiguous	0.5576	ambiguous	0.14	Stabilizing	1.0	D	0.72	deleterious	N	0.467110872	None	None	N
D/P	0.9598	likely_pathogenic	0.9804	pathogenic	0.054	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
D/Q	0.9172	likely_pathogenic	0.9585	pathogenic	0.146	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
D/R	0.944	likely_pathogenic	0.9708	pathogenic	0.449	Stabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
D/S	0.6094	likely_pathogenic	0.7705	pathogenic	0.011	Stabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
D/T	0.8651	likely_pathogenic	0.933	pathogenic	0.139	Stabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
D/V	0.8257	likely_pathogenic	0.9106	pathogenic	0.054	Stabilizing	1.0	D	0.704	prob.delet.	N	0.489227598	None	None	N
D/W	0.9884	likely_pathogenic	0.9937	pathogenic	-0.194	Destabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
D/Y	0.7615	likely_pathogenic	0.8515	pathogenic	-0.06	Destabilizing	1.0	D	0.753	deleterious	N	0.501851351	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.