TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19041	57346;57347;57348	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
N2AB	17400	52423;52424;52425	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
N2A	16473	49642;49643;49644	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
N2B	9976	30151;30152;30153	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
Novex-1	10101	30526;30527;30528	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
Novex-2	10168	30727;30728;30729	chr2:178598049;178598048;178598047	chr2:179462776;179462775;179462774
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: Fn3-26
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.4897
• 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/Q	rs1334101213	0.212	0.988	N	0.376	0.218	0.244539031024	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
K/Q	rs1334101213	0.212	0.988	N	0.376	0.218	0.244539031024	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs1334101213	0.212	0.988	N	0.376	0.218	0.244539031024	gnomAD-4.0.0	4.96182E-06	None	None	None	None	N	None	1.0686E-04	0	None	0	0	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
K/A	0.3036	likely_benign	0.3082	benign	0.055	Stabilizing	0.927	D	0.388	neutral	None	None	None	None	N
K/C	0.6953	likely_pathogenic	0.67	pathogenic	-0.366	Destabilizing	1.0	D	0.44	neutral	None	None	None	None	N
K/D	0.5409	ambiguous	0.5351	ambiguous	-0.304	Destabilizing	0.984	D	0.353	neutral	None	None	None	None	N
K/E	0.1976	likely_benign	0.1975	benign	-0.318	Destabilizing	0.959	D	0.419	neutral	N	0.449581651	None	None	N
K/F	0.7765	likely_pathogenic	0.7666	pathogenic	-0.277	Destabilizing	0.999	D	0.429	neutral	None	None	None	None	N
K/G	0.3936	ambiguous	0.3894	ambiguous	-0.073	Destabilizing	0.984	D	0.401	neutral	None	None	None	None	N
K/H	0.3581	ambiguous	0.3484	ambiguous	-0.183	Destabilizing	0.999	D	0.347	neutral	None	None	None	None	N
K/I	0.341	ambiguous	0.3323	benign	0.31	Stabilizing	0.988	D	0.44	neutral	N	0.479672484	None	None	N
K/L	0.4042	ambiguous	0.4029	ambiguous	0.31	Stabilizing	0.969	D	0.408	neutral	None	None	None	None	N
K/M	0.25	likely_benign	0.2459	benign	-0.075	Destabilizing	1.0	D	0.347	neutral	None	None	None	None	N
K/N	0.4327	ambiguous	0.4289	ambiguous	0.105	Stabilizing	0.979	D	0.355	neutral	N	0.479173839	None	None	N
K/P	0.7519	likely_pathogenic	0.734	pathogenic	0.249	Stabilizing	0.999	D	0.34	neutral	None	None	None	None	N
K/Q	0.1515	likely_benign	0.15	benign	-0.044	Destabilizing	0.988	D	0.376	neutral	N	0.483192792	None	None	N
K/R	0.0827	likely_benign	0.084	benign	-0.069	Destabilizing	0.068	N	0.204	neutral	N	0.477152254	None	None	N
K/S	0.3874	ambiguous	0.3864	ambiguous	-0.239	Destabilizing	0.939	D	0.377	neutral	None	None	None	None	N
K/T	0.1347	likely_benign	0.1415	benign	-0.141	Destabilizing	0.116	N	0.183	neutral	N	0.426667506	None	None	N
K/V	0.2958	likely_benign	0.2987	benign	0.249	Stabilizing	0.969	D	0.426	neutral	None	None	None	None	N
K/W	0.7432	likely_pathogenic	0.7123	pathogenic	-0.388	Destabilizing	1.0	D	0.533	neutral	None	None	None	None	N
K/Y	0.6473	likely_pathogenic	0.6167	pathogenic	-0.036	Destabilizing	0.999	D	0.422	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.