TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25821	77686;77687;77688	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
N2AB	24180	72763;72764;72765	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
N2A	23253	69982;69983;69984	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
N2B	16756	50491;50492;50493	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
Novex-1	16881	50866;50867;50868	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
Novex-2	16948	51067;51068;51069	chr2:178568671;178568670;178568669	chr2:179433398;179433397;179433396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-136
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1417
• 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
I/L	None	None	0.084	N	0.49	0.149	0.312306559268	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	5.66059E-05	0	None	0	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
I/A	0.5711	likely_pathogenic	0.6123	pathogenic	-2.453	Highly Destabilizing	0.404	N	0.708	prob.delet.	None	None	None	None	N
I/C	0.6953	likely_pathogenic	0.7072	pathogenic	-1.902	Destabilizing	0.973	D	0.767	deleterious	None	None	None	None	N
I/D	0.9832	likely_pathogenic	0.9866	pathogenic	-2.563	Highly Destabilizing	0.967	D	0.839	deleterious	None	None	None	None	N
I/E	0.9609	likely_pathogenic	0.9641	pathogenic	-2.461	Highly Destabilizing	0.906	D	0.829	deleterious	None	None	None	None	N
I/F	0.14	likely_benign	0.147	benign	-1.683	Destabilizing	0.642	D	0.73	prob.delet.	N	0.437325296	None	None	N
I/G	0.8879	likely_pathogenic	0.9097	pathogenic	-2.897	Highly Destabilizing	0.906	D	0.823	deleterious	None	None	None	None	N
I/H	0.806	likely_pathogenic	0.8214	pathogenic	-2.184	Highly Destabilizing	0.947	D	0.837	deleterious	None	None	None	None	N
I/K	0.8528	likely_pathogenic	0.8533	pathogenic	-1.892	Destabilizing	0.906	D	0.829	deleterious	None	None	None	None	N
I/L	0.1454	likely_benign	0.1519	benign	-1.228	Destabilizing	0.084	N	0.49	neutral	N	0.515650006	None	None	N
I/M	0.1746	likely_benign	0.1813	benign	-1.09	Destabilizing	0.782	D	0.695	prob.neutral	D	0.525213565	None	None	N
I/N	0.82	likely_pathogenic	0.8385	pathogenic	-1.953	Destabilizing	0.879	D	0.834	deleterious	N	0.514199654	None	None	N
I/P	0.9652	likely_pathogenic	0.9724	pathogenic	-1.612	Destabilizing	0.967	D	0.84	deleterious	None	None	None	None	N
I/Q	0.8677	likely_pathogenic	0.8767	pathogenic	-2.033	Highly Destabilizing	0.906	D	0.83	deleterious	None	None	None	None	N
I/R	0.7639	likely_pathogenic	0.771	pathogenic	-1.342	Destabilizing	0.906	D	0.827	deleterious	None	None	None	None	N
I/S	0.7015	likely_pathogenic	0.7264	pathogenic	-2.631	Highly Destabilizing	0.782	D	0.791	deleterious	D	0.523866845	None	None	N
I/T	0.5711	likely_pathogenic	0.6007	pathogenic	-2.398	Highly Destabilizing	0.505	D	0.754	deleterious	D	0.534678484	None	None	N
I/V	0.0567	likely_benign	0.0593	benign	-1.612	Destabilizing	0.001	N	0.223	neutral	N	0.408201962	None	None	N
I/W	0.882	likely_pathogenic	0.889	pathogenic	-1.908	Destabilizing	0.973	D	0.832	deleterious	None	None	None	None	N
I/Y	0.5664	likely_pathogenic	0.5798	pathogenic	-1.679	Destabilizing	0.01	N	0.503	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.