TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13751	41476;41477;41478	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
N2AB	12110	36553;36554;36555	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
N2A	11183	33772;33773;33774	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
N2B	4686	14281;14282;14283	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
Novex-1	4811	14656;14657;14658	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
Novex-2	4878	14857;14858;14859	chr2:178636476;178636475;178636474	chr2:179501203;179501202;179501201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-87
• Domain position: 68
• Structural Position: 148
• Q(SASA): 0.6294
• Predicted PPI site: I

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	rs1327407922	None	1.0	D	0.709	0.448	None	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1077	likely_benign	0.1227	benign	-0.184	Destabilizing	0.997	D	0.416	neutral	N	0.455196957	None	None	I
S/C	0.4067	ambiguous	0.4318	ambiguous	-0.292	Destabilizing	1.0	D	0.677	prob.neutral	D	0.646671908	None	None	I
S/D	0.5687	likely_pathogenic	0.6778	pathogenic	0.078	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	I
S/E	0.6615	likely_pathogenic	0.7636	pathogenic	-0.029	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	I
S/F	0.4601	ambiguous	0.5836	pathogenic	-0.903	Destabilizing	1.0	D	0.751	deleterious	N	0.51269937	None	None	I
S/G	0.1449	likely_benign	0.1446	benign	-0.244	Destabilizing	0.999	D	0.461	neutral	None	None	None	None	I
S/H	0.6323	likely_pathogenic	0.6991	pathogenic	-0.624	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
S/I	0.3721	ambiguous	0.4728	ambiguous	-0.159	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
S/K	0.8864	likely_pathogenic	0.9327	pathogenic	-0.348	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	I
S/L	0.1715	likely_benign	0.2145	benign	-0.159	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
S/M	0.3587	ambiguous	0.415	ambiguous	-0.052	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
S/N	0.2337	likely_benign	0.2873	benign	-0.1	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	I
S/P	0.3385	likely_benign	0.4432	ambiguous	-0.142	Destabilizing	1.0	D	0.709	prob.delet.	D	0.543220011	None	None	I
S/Q	0.7091	likely_pathogenic	0.7676	pathogenic	-0.341	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
S/R	0.842	likely_pathogenic	0.9009	pathogenic	-0.101	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
S/T	0.1269	likely_benign	0.1442	benign	-0.21	Destabilizing	0.999	D	0.455	neutral	N	0.44547735	None	None	I
S/V	0.3702	ambiguous	0.4625	ambiguous	-0.142	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
S/W	0.6359	likely_pathogenic	0.7192	pathogenic	-0.968	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
S/Y	0.4754	ambiguous	0.5711	pathogenic	-0.653	Destabilizing	1.0	D	0.747	deleterious	D	0.567436042	None	None	I

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.