TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24480	73663;73664;73665	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
N2AB	22839	68740;68741;68742	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
N2A	21912	65959;65960;65961	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
N2B	15415	46468;46469;46470	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
Novex-1	15540	46843;46844;46845	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
Novex-2	15607	47044;47045;47046	chr2:178572694;178572693;178572692	chr2:179437421;179437420;179437419
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: Ig-132
• Domain position: 50
• Structural Position: 134
• Q(SASA): 0.331
• 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/C	rs775608256	-0.325	1.0	D	0.665	0.525	0.72625753649	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	2.7908E-04	None	0	None	0	0	0
S/C	rs775608256	-0.325	1.0	D	0.665	0.525	0.72625753649	gnomAD-4.0.0	3.42166E-06	None	None	None	None	N	None	0	0	None	0	1.26078E-04	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
S/A	0.1565	likely_benign	0.1725	benign	-0.576	Destabilizing	0.997	D	0.578	neutral	N	0.501960159	None	None	N
S/C	0.268	likely_benign	0.2875	benign	-0.361	Destabilizing	1.0	D	0.665	neutral	D	0.523866757	None	None	N
S/D	0.8053	likely_pathogenic	0.8441	pathogenic	0.627	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
S/E	0.8967	likely_pathogenic	0.9172	pathogenic	0.593	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
S/F	0.589	likely_pathogenic	0.6608	pathogenic	-0.963	Destabilizing	1.0	D	0.696	prob.neutral	N	0.496861732	None	None	N
S/G	0.2122	likely_benign	0.2419	benign	-0.76	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
S/H	0.732	likely_pathogenic	0.77	pathogenic	-1.096	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
S/I	0.6053	likely_pathogenic	0.6577	pathogenic	-0.207	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
S/K	0.9684	likely_pathogenic	0.9772	pathogenic	-0.31	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
S/L	0.3016	likely_benign	0.3501	ambiguous	-0.207	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
S/M	0.4711	ambiguous	0.536	ambiguous	-0.145	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
S/N	0.435	ambiguous	0.4916	ambiguous	-0.188	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
S/P	0.9102	likely_pathogenic	0.9175	pathogenic	-0.299	Destabilizing	1.0	D	0.687	prob.neutral	D	0.523359778	None	None	N
S/Q	0.8335	likely_pathogenic	0.8613	pathogenic	-0.302	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
S/R	0.9462	likely_pathogenic	0.9576	pathogenic	-0.212	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
S/T	0.1556	likely_benign	0.1755	benign	-0.316	Destabilizing	0.999	D	0.589	neutral	N	0.514319068	None	None	N
S/V	0.5147	ambiguous	0.5646	pathogenic	-0.299	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
S/W	0.768	likely_pathogenic	0.7846	pathogenic	-0.945	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/Y	0.5242	ambiguous	0.582	pathogenic	-0.658	Destabilizing	1.0	D	0.699	prob.neutral	N	0.505142224	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.