TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27201	81826;81827;81828	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
N2AB	25560	76903;76904;76905	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
N2A	24633	74122;74123;74124	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
N2B	18136	54631;54632;54633	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
Novex-1	18261	55006;55007;55008	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
Novex-2	18328	55207;55208;55209	chr2:178564531;178564530;178564529	chr2:179429258;179429257;179429256
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: Fn3-86
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7563
• Predicted PPI site: I

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/N	None	None	0.491	N	0.403	0.162	0.195762928549	gnomAD-4.0.0	1.59297E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86022E-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	0.4555	ambiguous	0.388	ambiguous	-0.131	Destabilizing	0.007	N	0.16	neutral	None	None	None	None	I
K/C	0.7688	likely_pathogenic	0.7444	pathogenic	-0.183	Destabilizing	0.991	D	0.465	neutral	None	None	None	None	I
K/D	0.8033	likely_pathogenic	0.7766	pathogenic	0.15	Stabilizing	0.722	D	0.499	neutral	None	None	None	None	I
K/E	0.3851	ambiguous	0.3274	benign	0.154	Stabilizing	0.491	N	0.371	neutral	N	0.48923333	None	None	I
K/F	0.8603	likely_pathogenic	0.8229	pathogenic	-0.397	Destabilizing	0.818	D	0.493	neutral	None	None	None	None	I
K/G	0.686	likely_pathogenic	0.6231	pathogenic	-0.332	Destabilizing	0.561	D	0.499	neutral	None	None	None	None	I
K/H	0.4348	ambiguous	0.4155	ambiguous	-0.71	Destabilizing	0.901	D	0.474	neutral	None	None	None	None	I
K/I	0.4231	ambiguous	0.371	ambiguous	0.321	Stabilizing	0.326	N	0.525	neutral	N	0.476092499	None	None	I
K/L	0.4351	ambiguous	0.3719	ambiguous	0.321	Stabilizing	0.004	N	0.205	neutral	None	None	None	None	I
K/M	0.3136	likely_benign	0.2573	benign	0.304	Stabilizing	0.818	D	0.482	neutral	None	None	None	None	I
K/N	0.657	likely_pathogenic	0.5996	pathogenic	0.256	Stabilizing	0.491	N	0.403	neutral	N	0.478294545	None	None	I
K/P	0.5699	likely_pathogenic	0.5811	pathogenic	0.199	Stabilizing	0.901	D	0.494	neutral	None	None	None	None	I
K/Q	0.2093	likely_benign	0.1811	benign	0.03	Stabilizing	0.491	N	0.425	neutral	N	0.470052111	None	None	I
K/R	0.0832	likely_benign	0.079	benign	-0.005	Destabilizing	0.003	N	0.214	neutral	N	0.480328632	None	None	I
K/S	0.6147	likely_pathogenic	0.5595	ambiguous	-0.3	Destabilizing	0.209	N	0.359	neutral	None	None	None	None	I
K/T	0.3406	ambiguous	0.2895	benign	-0.143	Destabilizing	0.013	N	0.227	neutral	N	0.503434778	None	None	I
K/V	0.3473	ambiguous	0.3061	benign	0.199	Stabilizing	0.017	N	0.236	neutral	None	None	None	None	I
K/W	0.8632	likely_pathogenic	0.8414	pathogenic	-0.36	Destabilizing	0.991	D	0.479	neutral	None	None	None	None	I
K/Y	0.7563	likely_pathogenic	0.7174	pathogenic	0.002	Stabilizing	0.965	D	0.501	neutral	None	None	None	None	I

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.