TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14556	43891;43892;43893	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
N2AB	12915	38968;38969;38970	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
N2A	11988	36187;36188;36189	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
N2B	5491	16696;16697;16698	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
Novex-1	5616	17071;17072;17073	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
Novex-2	5683	17272;17273;17274	chr2:178632228;178632227;178632226	chr2:179496955;179496954;179496953
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: Ig-96
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.3333
• 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/E	rs1553738199	None	0.201	N	0.445	0.249	0.297031009988	gnomAD-4.0.0	3.21266E-06	None	None	None	None	N	None	0	2.32396E-05	None	0	0	None	0	0	0	1.45679E-05	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	0.3869	ambiguous	0.382	ambiguous	-0.617	Destabilizing	0.399	N	0.476	neutral	None	None	None	None	N
K/C	0.7162	likely_pathogenic	0.7181	pathogenic	-0.815	Destabilizing	0.982	D	0.665	neutral	None	None	None	None	N
K/D	0.5638	ambiguous	0.5481	ambiguous	-0.132	Destabilizing	0.7	D	0.524	neutral	None	None	None	None	N
K/E	0.1547	likely_benign	0.1523	benign	-0.082	Destabilizing	0.201	N	0.445	neutral	N	0.505384125	None	None	N
K/F	0.7525	likely_pathogenic	0.7238	pathogenic	-0.862	Destabilizing	0.947	D	0.666	neutral	None	None	None	None	N
K/G	0.4578	ambiguous	0.4375	ambiguous	-0.874	Destabilizing	0.399	N	0.537	neutral	None	None	None	None	N
K/H	0.2888	likely_benign	0.2655	benign	-1.332	Destabilizing	0.947	D	0.557	neutral	None	None	None	None	N
K/I	0.3691	ambiguous	0.3597	ambiguous	0.008	Stabilizing	0.781	D	0.692	prob.neutral	D	0.543975602	None	None	N
K/L	0.3754	ambiguous	0.3594	ambiguous	0.008	Stabilizing	0.399	N	0.537	neutral	None	None	None	None	N
K/M	0.2638	likely_benign	0.2636	benign	0.121	Stabilizing	0.982	D	0.557	neutral	None	None	None	None	N
K/N	0.3757	ambiguous	0.3522	ambiguous	-0.218	Destabilizing	0.638	D	0.488	neutral	N	0.508103218	None	None	N
K/P	0.8028	likely_pathogenic	0.8079	pathogenic	-0.173	Destabilizing	0.826	D	0.575	neutral	None	None	None	None	N
K/Q	0.1391	likely_benign	0.1307	benign	-0.523	Destabilizing	0.015	N	0.227	neutral	D	0.560200856	None	None	N
K/R	0.0675	likely_benign	0.0691	benign	-0.266	Destabilizing	0.002	N	0.289	neutral	N	0.489313456	None	None	N
K/S	0.4014	ambiguous	0.3724	ambiguous	-0.942	Destabilizing	0.399	N	0.447	neutral	None	None	None	None	N
K/T	0.1695	likely_benign	0.1724	benign	-0.715	Destabilizing	0.638	D	0.517	neutral	N	0.510762249	None	None	N
K/V	0.3801	ambiguous	0.3795	ambiguous	-0.173	Destabilizing	0.7	D	0.589	neutral	None	None	None	None	N
K/W	0.6625	likely_pathogenic	0.6513	pathogenic	-0.696	Destabilizing	0.982	D	0.655	neutral	None	None	None	None	N
K/Y	0.5766	likely_pathogenic	0.5727	pathogenic	-0.309	Destabilizing	0.826	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.