ClinVar Miner

Submissions for variant NM_001198800.3(ASCC1):c.328C>T (p.Arg110Ter)

gnomAD frequency: 0.00002  dbSNP: rs866050664
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001858633 SCV002232686 pathogenic not provided 2023-09-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 801335). This variant is also known as p.Arg138*. This premature translational stop signal has been observed in individual(s) with spinal muscular atrophy with congenital bone fractures (PMID: 30327447). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change creates a premature translational stop signal (p.Arg110*) in the ASCC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ASCC1 are known to be pathogenic (PMID: 30327447).
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire RCV004586997 SCV005038494 pathogenic Centronuclear myopathy 2024-03-01 criteria provided, single submitter research PVS1+PM2+PM4+PP3+PP5
Neuberg Centre For Genomic Medicine, NCGM RCV000986102 SCV005400777 pathogenic Spinal muscular atrophy with congenital bone fractures 2 2023-06-22 criteria provided, single submitter clinical testing The observed stop gain c.328C>T(p.Arg110Ter) variant in ASCC1 has been reported in homozygous state in individuals affected with ASCC1 related disorder (Rosano KK, et. al., 2021). It has also been observed to segregate with disease in related individuals (Böhm J, et. al., 2019). This variant is present with an allele frequency of 0.002% in gnomAD Exomes database. This variant has been reported to the ClinVar database as Pathogenic. Computational evidence (MutationTaster - disease causing) predict damaging effect on protein structure and function for this variant. The nucleotide change c.328C>T in ASCC1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing (Böhm J, et. al., 2019). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001858633 SCV005401452 pathogenic not provided 2024-05-15 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 34302381, 30327447)
OMIM RCV000986102 SCV001134940 pathogenic Spinal muscular atrophy with congenital bone fractures 2 2020-01-03 no assertion criteria provided literature only

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