Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Integrated Genetics/Laboratory Corporation of America | RCV000586221 | SCV000696579 | uncertain significance | not provided | 2016-10-24 | criteria provided, single submitter | clinical testing | Variant summary: The SMN1 c.835-3C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, Vezain_2011 showed that c.835-3C>T leads to 20% of exon 7 skipping in SMN1 mRNA using minigene assay. In addition, this paper showed full length/exon7 skipped SMN1 mRNA ratio in a patient with mild SMA phenotype, who also carries an exon 7 deletion allele, is higher than the controls with no SMN1 copy and lower than the control with one SMN1 copy. These results further demonstrate that the variant of interest induces exon 7 skipping. However, the pathogenic role of this effect is not clear due to small sample size of patients and lack of additional functional studies. This variant was found in 2/120368 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic SMN1 variant (0.0025). Since only one SMA patient has been reported to carry this variant and the pathogenic role of small amount of exon 7 skipping is not clear, this variant is classified as VUS-possibly pathogenic. |
| Molecular Diagnostics Lab, |
RCV000785808 | SCV000924376 | pathogenic | Adult spinal muscular atrophy | 2016-03-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000798141 | SCV000937741 | uncertain significance | Spinal muscular atrophy | 2018-10-10 | criteria provided, single submitter | clinical testing |