TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23256	69991;69992;69993	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
N2AB	21615	65068;65069;65070	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
N2A	20688	62287;62288;62289	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
N2B	14191	42796;42797;42798	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
Novex-1	14316	43171;43172;43173	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
Novex-2	14383	43372;43373;43374	chr2:178576366;178576365;178576364	chr2:179441093;179441092;179441091
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-57
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1686
• 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
S/P	rs1710100033	None	0.984	D	0.637	0.459	0.363751660372	gnomAD-4.0.0	2.84574E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.66584E-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
S/A	0.2488	likely_benign	0.2644	benign	-0.789	Destabilizing	0.64	D	0.391	neutral	N	0.490129193	None	None	N
S/C	0.2746	likely_benign	0.2856	benign	-0.907	Destabilizing	0.999	D	0.645	neutral	N	0.499398811	None	None	N
S/D	0.8767	likely_pathogenic	0.8547	pathogenic	-1.414	Destabilizing	0.919	D	0.498	neutral	None	None	None	None	N
S/E	0.8829	likely_pathogenic	0.8739	pathogenic	-1.356	Destabilizing	0.919	D	0.487	neutral	None	None	None	None	N
S/F	0.5242	ambiguous	0.5092	ambiguous	-1.025	Destabilizing	0.984	D	0.729	prob.delet.	N	0.499145321	None	None	N
S/G	0.3309	likely_benign	0.3201	benign	-1.051	Destabilizing	0.919	D	0.476	neutral	None	None	None	None	N
S/H	0.6869	likely_pathogenic	0.6559	pathogenic	-1.532	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/I	0.666	likely_pathogenic	0.6674	pathogenic	-0.183	Destabilizing	0.976	D	0.669	neutral	None	None	None	None	N
S/K	0.9622	likely_pathogenic	0.9565	pathogenic	-0.702	Destabilizing	0.919	D	0.494	neutral	None	None	None	None	N
S/L	0.3363	likely_benign	0.3557	ambiguous	-0.183	Destabilizing	0.851	D	0.584	neutral	None	None	None	None	N
S/M	0.3466	ambiguous	0.3383	benign	0.015	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	N
S/N	0.4584	ambiguous	0.439	ambiguous	-1.032	Destabilizing	0.919	D	0.509	neutral	None	None	None	None	N
S/P	0.9941	likely_pathogenic	0.9941	pathogenic	-0.353	Destabilizing	0.984	D	0.637	neutral	D	0.529922555	None	None	N
S/Q	0.8552	likely_pathogenic	0.8461	pathogenic	-1.183	Destabilizing	0.988	D	0.551	neutral	None	None	None	None	N
S/R	0.95	likely_pathogenic	0.945	pathogenic	-0.639	Destabilizing	0.976	D	0.645	neutral	None	None	None	None	N
S/T	0.0905	likely_benign	0.0817	benign	-0.86	Destabilizing	0.016	N	0.138	neutral	N	0.484585233	None	None	N
S/V	0.5793	likely_pathogenic	0.5713	pathogenic	-0.353	Destabilizing	0.851	D	0.589	neutral	None	None	None	None	N
S/W	0.6978	likely_pathogenic	0.6712	pathogenic	-1.097	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
S/Y	0.3951	ambiguous	0.3803	ambiguous	-0.734	Destabilizing	0.995	D	0.727	prob.delet.	N	0.490889661	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.