TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33615	101068;101069;101070	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
N2AB	31974	96145;96146;96147	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
N2A	31047	93364;93365;93366	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
N2B	24550	73873;73874;73875	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
Novex-1	24675	74248;74249;74250	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
Novex-2	24742	74449;74450;74451	chr2:178535772;178535771;178535770	chr2:179400499;179400498;179400497
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-159
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1142
• 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/V	None	None	0.987	N	0.368	0.342	0.602107291794	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85853E-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
I/A	0.9873	likely_pathogenic	0.9697	pathogenic	-2.146	Highly Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
I/C	0.9879	likely_pathogenic	0.9751	pathogenic	-1.712	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9991	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/E	0.9984	likely_pathogenic	0.9961	pathogenic	-1.818	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/F	0.6902	likely_pathogenic	0.4811	ambiguous	-1.309	Destabilizing	1.0	D	0.809	deleterious	N	0.467380765	None	None	N
I/G	0.9988	likely_pathogenic	0.9965	pathogenic	-2.64	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/H	0.9975	likely_pathogenic	0.994	pathogenic	-1.971	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/K	0.9965	likely_pathogenic	0.9922	pathogenic	-1.704	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
I/L	0.3044	likely_benign	0.22	benign	-0.71	Destabilizing	0.983	D	0.397	neutral	N	0.417952022	None	None	N
I/M	0.403	ambiguous	0.2733	benign	-0.857	Destabilizing	1.0	D	0.754	deleterious	N	0.502120562	None	None	N
I/N	0.9956	likely_pathogenic	0.9903	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.877	deleterious	N	0.508876374	None	None	N
I/P	0.9992	likely_pathogenic	0.998	pathogenic	-1.173	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/Q	0.9959	likely_pathogenic	0.9909	pathogenic	-1.902	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/R	0.9943	likely_pathogenic	0.9877	pathogenic	-1.687	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/S	0.994	likely_pathogenic	0.9865	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.862	deleterious	N	0.508876374	None	None	N
I/T	0.9893	likely_pathogenic	0.9763	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.814	deleterious	N	0.497101995	None	None	N
I/V	0.1893	likely_benign	0.1568	benign	-1.173	Destabilizing	0.987	D	0.368	neutral	N	0.500504409	None	None	N
I/W	0.9932	likely_pathogenic	0.9827	pathogenic	-1.486	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
I/Y	0.9813	likely_pathogenic	0.9583	pathogenic	-1.255	Destabilizing	1.0	D	0.809	deleterious	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.