TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35628	107107;107108;107109	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
N2AB	33987	102184;102185;102186	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
N2A	33060	99403;99404;99405	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
N2B	26563	79912;79913;79914	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
Novex-1	26688	80287;80288;80289	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
Novex-2	26755	80488;80489;80490	chr2:178528869;178528868;178528867	chr2:179393596;179393595;179393594
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-167
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1222
• 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
A/G	rs748131753	-1.565	1.0	N	0.728	0.383	0.331619326243	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
A/G	rs748131753	-1.565	1.0	N	0.728	0.383	0.331619326243	gnomAD-4.0.0	6.84145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99399E-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
A/C	0.8193	likely_pathogenic	0.8379	pathogenic	-1.131	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/D	0.9268	likely_pathogenic	0.9633	pathogenic	-1.954	Destabilizing	1.0	D	0.909	deleterious	N	0.463598593	None	None	N
A/E	0.8684	likely_pathogenic	0.9214	pathogenic	-1.916	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
A/F	0.8279	likely_pathogenic	0.88	pathogenic	-1.125	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
A/G	0.2611	likely_benign	0.2913	benign	-1.482	Destabilizing	1.0	D	0.728	prob.delet.	N	0.463425235	None	None	N
A/H	0.9581	likely_pathogenic	0.9762	pathogenic	-1.729	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
A/I	0.6996	likely_pathogenic	0.721	pathogenic	-0.328	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
A/K	0.9531	likely_pathogenic	0.9741	pathogenic	-1.352	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/L	0.5762	likely_pathogenic	0.6207	pathogenic	-0.328	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/M	0.6526	likely_pathogenic	0.6924	pathogenic	-0.229	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
A/N	0.8577	likely_pathogenic	0.9109	pathogenic	-1.25	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
A/P	0.9418	likely_pathogenic	0.967	pathogenic	-0.558	Destabilizing	1.0	D	0.886	deleterious	N	0.463598593	None	None	N
A/Q	0.8919	likely_pathogenic	0.9255	pathogenic	-1.335	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
A/R	0.926	likely_pathogenic	0.9555	pathogenic	-1.081	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/S	0.2451	likely_benign	0.2887	benign	-1.623	Destabilizing	1.0	D	0.723	prob.delet.	N	0.463251876	None	None	N
A/T	0.2679	likely_benign	0.308	benign	-1.486	Destabilizing	1.0	D	0.861	deleterious	N	0.463078518	None	None	N
A/V	0.3432	ambiguous	0.3679	ambiguous	-0.558	Destabilizing	1.0	D	0.777	deleterious	N	0.459958068	None	None	N
A/W	0.977	likely_pathogenic	0.9866	pathogenic	-1.622	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
A/Y	0.9075	likely_pathogenic	0.9433	pathogenic	-1.181	Destabilizing	1.0	D	0.927	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.