TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30810	92653;92654;92655	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
N2AB	29169	87730;87731;87732	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
N2A	28242	84949;84950;84951	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
N2B	21745	65458;65459;65460	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
Novex-1	21870	65833;65834;65835	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
Novex-2	21937	66034;66035;66036	chr2:178549198;178549197;178549196	chr2:179413925;179413924;179413923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-112
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.1719
• 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/L	rs1021262891	None	0.999	D	0.712	0.471	0.68573823706	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/L	rs1021262891	None	0.999	D	0.712	0.471	0.68573823706	gnomAD-4.0.0	6.08976E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.22956E-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	0.5319	ambiguous	0.5669	pathogenic	-0.479	Destabilizing	0.994	D	0.696	prob.delet.	N	0.500301777	None	None	N
S/C	0.3478	ambiguous	0.4507	ambiguous	-0.128	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
S/D	0.9831	likely_pathogenic	0.9821	pathogenic	-0.652	Destabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	N
S/E	0.9932	likely_pathogenic	0.9938	pathogenic	-0.464	Destabilizing	0.998	D	0.695	prob.delet.	None	None	None	None	N
S/F	0.9789	likely_pathogenic	0.9794	pathogenic	-0.333	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
S/G	0.4055	ambiguous	0.3873	ambiguous	-0.873	Destabilizing	0.998	D	0.691	prob.delet.	None	None	None	None	N
S/H	0.9783	likely_pathogenic	0.9795	pathogenic	-1.12	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/I	0.9521	likely_pathogenic	0.9637	pathogenic	0.517	Stabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
S/K	0.9989	likely_pathogenic	0.9989	pathogenic	0.152	Stabilizing	0.998	D	0.705	prob.delet.	None	None	None	None	N
S/L	0.8278	likely_pathogenic	0.8473	pathogenic	0.517	Stabilizing	0.999	D	0.712	prob.delet.	D	0.523725631	None	None	N
S/M	0.898	likely_pathogenic	0.919	pathogenic	0.296	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
S/N	0.9255	likely_pathogenic	0.9232	pathogenic	-0.469	Destabilizing	0.998	D	0.725	deleterious	None	None	None	None	N
S/P	0.9766	likely_pathogenic	0.9761	pathogenic	0.221	Stabilizing	0.999	D	0.831	deleterious	D	0.529295038	None	None	N
S/Q	0.9888	likely_pathogenic	0.9901	pathogenic	-0.223	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
S/R	0.9976	likely_pathogenic	0.9976	pathogenic	-0.239	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
S/T	0.2334	likely_benign	0.254	benign	-0.201	Destabilizing	0.997	D	0.697	prob.delet.	N	0.517435865	None	None	N
S/V	0.911	likely_pathogenic	0.933	pathogenic	0.221	Stabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
S/W	0.9816	likely_pathogenic	0.9813	pathogenic	-0.581	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
S/Y	0.9748	likely_pathogenic	0.9749	pathogenic	-0.083	Destabilizing	0.999	D	0.875	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.