TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21482	64669;64670;64671	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
N2AB	19841	59746;59747;59748	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
N2A	18914	56965;56966;56967	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
N2B	12417	37474;37475;37476	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
Novex-1	12542	37849;37850;37851	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
Novex-2	12609	38050;38051;38052	chr2:178585300;178585299;178585298	chr2:179450027;179450026;179450025
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-124
• Domain position: 14
• Structural Position: 25
• Q(SASA): 0.379
• 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	rs113935908	None	0.454	N	0.469	0.084	0.165133752707	gnomAD-4.0.0	2.74144E-06	None	None	None	None	N	None	3.00788E-05	0	None	0	0	None	0	0	1.80082E-06	0	1.65948E-05
K/N	rs1232234781	-0.266	0.801	N	0.377	0.141	0.149567049428	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
K/N	rs1232234781	-0.266	0.801	N	0.377	0.141	0.149567049428	gnomAD-4.0.0	1.59755E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86783E-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
K/A	0.4511	ambiguous	0.3893	ambiguous	-0.175	Destabilizing	0.525	D	0.363	neutral	None	None	None	None	N
K/C	0.6862	likely_pathogenic	0.6502	pathogenic	-0.31	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	N
K/D	0.5444	ambiguous	0.4703	ambiguous	0.11	Stabilizing	0.842	D	0.343	neutral	None	None	None	None	N
K/E	0.2118	likely_benign	0.1753	benign	0.164	Stabilizing	0.454	N	0.469	neutral	N	0.423034476	None	None	N
K/F	0.8779	likely_pathogenic	0.8589	pathogenic	-0.143	Destabilizing	0.991	D	0.445	neutral	None	None	None	None	N
K/G	0.4623	ambiguous	0.3973	ambiguous	-0.453	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	N
K/H	0.3087	likely_benign	0.2807	benign	-0.739	Destabilizing	0.974	D	0.341	neutral	None	None	None	None	N
K/I	0.6415	likely_pathogenic	0.5918	pathogenic	0.5	Stabilizing	0.966	D	0.444	neutral	N	0.459415097	None	None	N
K/L	0.5248	ambiguous	0.465	ambiguous	0.5	Stabilizing	0.842	D	0.406	neutral	None	None	None	None	N
K/M	0.3471	ambiguous	0.3164	benign	0.233	Stabilizing	0.974	D	0.339	neutral	None	None	None	None	N
K/N	0.4171	ambiguous	0.3664	ambiguous	-0.022	Destabilizing	0.801	D	0.377	neutral	N	0.457747269	None	None	N
K/P	0.958	likely_pathogenic	0.9369	pathogenic	0.305	Stabilizing	0.974	D	0.317	neutral	None	None	None	None	N
K/Q	0.1195	likely_benign	0.109	benign	-0.121	Destabilizing	0.051	N	0.299	neutral	N	0.437582641	None	None	N
K/R	0.0964	likely_benign	0.0908	benign	-0.251	Destabilizing	0.669	D	0.433	neutral	N	0.467156186	None	None	N
K/S	0.4086	ambiguous	0.3564	ambiguous	-0.568	Destabilizing	0.08	N	0.191	neutral	None	None	None	None	N
K/T	0.2413	likely_benign	0.2163	benign	-0.335	Destabilizing	0.669	D	0.366	neutral	N	0.456843192	None	None	N
K/V	0.5228	ambiguous	0.4782	ambiguous	0.305	Stabilizing	0.915	D	0.401	neutral	None	None	None	None	N
K/W	0.8361	likely_pathogenic	0.8163	pathogenic	-0.111	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
K/Y	0.6984	likely_pathogenic	0.6534	pathogenic	0.211	Stabilizing	0.991	D	0.423	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.