Submissions for variant NM_170707.4(LMNA):c.978_979del (p.Leu327fs)

dbSNP: rs794728610

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182391	SCV000234729	pathogenic	not provided	2013-07-31	criteria provided, single submitter	clinical testing	Although the c.978_979delAC mutation in the LMNA gene has not been reported to our knowledge, this mutation causes a shift in reading frame starting at residue Leucine 327, changing it to a Glycine, and creating a premature stop codon at position 3 of the new reading frame, denoted p.Leu327GlyfsX3. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the LMNA gene have been reported in association with cardiomyopathy/laminopathy. Therefore, the presence of this mutation is consistent with an autosomal dominant form of DCM/laminopathy.
Invitae	RCV001382584	SCV001581424	pathogenic	Charcot-Marie-Tooth disease type 2	2020-07-22	criteria provided, single submitter	clinical testing	Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Leu327Glyfs*3) in the LMNA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LMNA-related conditions. ClinVar contains an entry for this variant (Variation ID: 200961).