TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30291	91096;91097;91098	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
N2AB	28650	86173;86174;86175	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
N2A	27723	83392;83393;83394	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
N2B	21226	63901;63902;63903	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
Novex-1	21351	64276;64277;64278	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
Novex-2	21418	64477;64478;64479	chr2:178552029;178552028;178552027	chr2:179416756;179416755;179416754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-108
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4821
• 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
K/R	rs1575514675	None	0.999	N	0.687	0.347	0.292787519742	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	4.77236E-05	0	None	0	0	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
K/A	0.6661	likely_pathogenic	0.5485	ambiguous	-0.191	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
K/C	0.8842	likely_pathogenic	0.8404	pathogenic	-0.233	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
K/D	0.8868	likely_pathogenic	0.8278	pathogenic	0.042	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/E	0.41	ambiguous	0.3054	benign	0.086	Stabilizing	0.999	D	0.689	prob.neutral	N	0.406348162	None	None	N
K/F	0.9646	likely_pathogenic	0.9455	pathogenic	-0.168	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/G	0.7936	likely_pathogenic	0.6939	pathogenic	-0.47	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/H	0.6236	likely_pathogenic	0.5648	pathogenic	-0.824	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/I	0.7644	likely_pathogenic	0.6691	pathogenic	0.489	Stabilizing	1.0	D	0.661	neutral	N	0.466879332	None	None	N
K/L	0.7252	likely_pathogenic	0.6347	pathogenic	0.489	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/M	0.5527	ambiguous	0.4514	ambiguous	0.327	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
K/N	0.8087	likely_pathogenic	0.715	pathogenic	0.007	Stabilizing	1.0	D	0.671	neutral	N	0.460433363	None	None	N
K/P	0.7404	likely_pathogenic	0.6324	pathogenic	0.292	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/Q	0.2612	likely_benign	0.2142	benign	-0.136	Destabilizing	1.0	D	0.681	prob.neutral	N	0.438884655	None	None	N
K/R	0.1003	likely_benign	0.0956	benign	-0.292	Destabilizing	0.999	D	0.687	prob.neutral	N	0.449563008	None	None	N
K/S	0.7875	likely_pathogenic	0.6852	pathogenic	-0.541	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/T	0.4609	ambiguous	0.3577	ambiguous	-0.322	Destabilizing	1.0	D	0.632	neutral	N	0.377932196	None	None	N
K/V	0.699	likely_pathogenic	0.6108	pathogenic	0.292	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
K/W	0.9382	likely_pathogenic	0.9145	pathogenic	-0.117	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.9114	likely_pathogenic	0.8734	pathogenic	0.198	Stabilizing	1.0	D	0.621	neutral	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.