TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17716	53371;53372;53373	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
N2AB	16075	48448;48449;48450	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
N2A	15148	45667;45668;45669	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
N2B	8651	26176;26177;26178	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
Novex-1	8776	26551;26552;26553	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
Novex-2	8843	26752;26753;26754	chr2:178607542;178607541;178607540	chr2:179472269;179472268;179472267
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-113
• Domain position: 40
• Structural Position: 109
• Q(SASA): 0.6279
• 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
D/N	rs1576363473	None	0.638	N	0.515	0.205	0.219573609325	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07555E-04	0
D/N	rs1576363473	None	0.638	N	0.515	0.205	0.219573609325	gnomAD-4.0.0	6.58033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07555E-04	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
D/A	0.146	likely_benign	0.1136	benign	-0.005	Destabilizing	0.201	N	0.44	neutral	N	0.488147534	None	None	N
D/C	0.5239	ambiguous	0.5101	ambiguous	-0.048	Destabilizing	0.982	D	0.647	neutral	None	None	None	None	N
D/E	0.1213	likely_benign	0.0916	benign	-0.224	Destabilizing	0.001	N	0.235	neutral	N	0.460267499	None	None	N
D/F	0.5767	likely_pathogenic	0.5174	ambiguous	-0.12	Destabilizing	0.982	D	0.596	neutral	None	None	None	None	N
D/G	0.1233	likely_benign	0.1042	benign	-0.12	Destabilizing	0.334	N	0.489	neutral	N	0.464691884	None	None	N
D/H	0.2607	likely_benign	0.2398	benign	0.403	Stabilizing	0.931	D	0.551	neutral	N	0.462315159	None	None	N
D/I	0.3508	ambiguous	0.3029	benign	0.231	Stabilizing	0.826	D	0.608	neutral	None	None	None	None	N
D/K	0.2425	likely_benign	0.231	benign	0.429	Stabilizing	0.25	N	0.488	neutral	None	None	None	None	N
D/L	0.3273	likely_benign	0.2916	benign	0.231	Stabilizing	0.7	D	0.59	neutral	None	None	None	None	N
D/M	0.5372	ambiguous	0.4472	ambiguous	0.102	Stabilizing	0.982	D	0.613	neutral	None	None	None	None	N
D/N	0.0967	likely_benign	0.0862	benign	0.262	Stabilizing	0.638	D	0.515	neutral	N	0.510504319	None	None	N
D/P	0.6086	likely_pathogenic	0.557	ambiguous	0.171	Stabilizing	0.826	D	0.537	neutral	None	None	None	None	N
D/Q	0.2429	likely_benign	0.2145	benign	0.257	Stabilizing	0.539	D	0.537	neutral	None	None	None	None	N
D/R	0.3429	ambiguous	0.3299	benign	0.627	Stabilizing	0.539	D	0.533	neutral	None	None	None	None	N
D/S	0.1121	likely_benign	0.0908	benign	0.143	Stabilizing	0.25	N	0.473	neutral	None	None	None	None	N
D/T	0.2022	likely_benign	0.1607	benign	0.235	Stabilizing	0.7	D	0.517	neutral	None	None	None	None	N
D/V	0.1992	likely_benign	0.1694	benign	0.171	Stabilizing	0.638	D	0.597	neutral	N	0.477963879	None	None	N
D/W	0.8034	likely_pathogenic	0.7957	pathogenic	-0.084	Destabilizing	0.982	D	0.656	neutral	None	None	None	None	N
D/Y	0.2149	likely_benign	0.2283	benign	0.102	Stabilizing	0.976	D	0.594	neutral	N	0.473671465	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.